ABSTRACT
A highly efficient synthesis of small pseudopeptidic cages from simple precursors has been achieved by the triple S(N)2 reaction between tripodal tris(amido amines) and several 1,3,5-tris(bromomethyl)benzene electrophiles. The success of the macrobicyclization strongly depends on the central triamine scaffold, which dictates the correct preorganization of the intermediates. The chloride binding properties of the protonated pseudopeptidic cages have been studied in the solid state (by X-ray diffraction) as well as in solution (by NMR spectroscopy and ESI-MS) and in the gas phase (by collision-induced dissociation (CID)-MS). The crystal structure of the HCl salts of several cages show a chloride partially or completely caged within the cavity of the macrobicycle. Both the amino acid side chain and the substitution at the aromatic tripodal ring have an effect on the chloride binding ability. The cages derived from the 1,3,5-benzene moiety show low affinity, whereas the triple substitution in the ring (either with Me or Et) increases the chloride binding by one order of magnitude. Besides, the cages derived from aliphatic amino acids display a stronger interaction than those derived from phenylalanine. The basis for the different mode of binding depending on the receptor structure is proposed according to the structural data (X-ray and NMR spectroscopy). Finally, the transport of the chloride anion through lipid bilayers has been studied for selected cages. Despite the important differences in the chloride binding, the transport properties are better correlated with the lipophilicity of the molecules. Therefore, the pseudopeptidic cages sharing the same binding motif for chloride rendered very different interaction and transport properties depending on the peripheral substitution.
Subject(s)
Amino Acids/chemistry , Chlorides/chemistry , Ethylenediamines/chemistry , Macrocyclic Compounds/chemical synthesis , Peptidomimetics/chemical synthesis , Binding Sites , Bridged Bicyclo Compounds/chemistry , Cyclization , Drug Compounding , Ion Transport , Lipid Bilayers/chemistry , Liposomes , Macrocyclic Compounds/chemistry , Models, Molecular , Molecular Structure , Peptidomimetics/chemistry , Solutions , Spectrometry, Mass, Electrospray Ionization , X-Ray DiffractionABSTRACT
The formation of soluble nano-spheres or stable hydrogels through the self-assembling of a simple gemini amphiphilic pseudopeptide can be controlled by the tuning of the hydrophilic/hydrophobic interactions in aqueous medium.
Subject(s)
Hydrogels/chemistry , Nanostructures/chemistry , Peptides/chemistry , Surface-Active Agents/chemistry , Hydrophobic and Hydrophilic Interactions , Nanostructures/ultrastructure , SolubilityABSTRACT
The use of pseudopeptidic gemini surfactants as stabilizers of hydrophobic quantum dots in water is discussed. Compound 1a acts as an intercalator with hydrophobic ligands of QDs transferring them from toluene to pure water yielding a fluorescent nanoparticle resistant to quenching by chloride anion (up to 0.1 M).
Subject(s)
Cadmium Compounds/chemistry , Calcitriol/analogs & derivatives , Quantum Dots , Selenium Compounds/chemistry , Sulfides/chemistry , Surface-Active Agents/chemistry , Zinc Compounds/chemistry , Calcitriol/chemistry , Chlorides/chemistry , Hydrophobic and Hydrophilic Interactions , Spectrometry, Fluorescence , Toluene/chemistry , Water/chemistryABSTRACT
The anion-templated synthesis of different pseudopeptidic macrocycles has been studied in detail by using a multidisciplinary approach. The reaction between an open-chain pseudopeptidic diamine and the appropriate dialdehyde is highly affected by the presence of the best fitting anionic template. The formation of the corresponding macrocyclic tetraimino-template supramolecular complex is demonstrated by NMR (ROESY and PGSE) and mass spectrometry (ESI-TOF). These supramolecular complexes can be easily reduced to the corresponding more stable tetraamine macrocycles. Accordingly, we have used this reaction to efficiently synthesize a family of new pseudopeptidic macrocycles in a one-pot two-steps anion-templated reductive amination reaction, which comprises a multicomponent macrocyclization through the selective formation of four chemical bonds to yield a unique macrocyclic structure. Different variables like the aliphatic spacer between amino acidic moieties, geometry of the dialdehyde, and structure of the amino acid side chains were thoroughly studied, and their effect in the formation and stability of the supramolecular complexes discussed. The conformational preorganization induced by the template has been monitored by circular dichroism, reflecting the differences observed in the isolated yields, as well as by NMR spectroscopy. This effect has been also supported by molecular modeling. All the experimental and theoretical techniques were strongly consistent and reflected the same trends by comparing the different structural variables introduced in the system.
