Incorporation of a calixarene-based glucose functionalised bolaamphiphile into lipid bilayers for multivalent lectin recognition.

The synthesis, characterization and inclusion in liposomes of a glucosylated bolaamphiphile built on a calix[4]arene scaffold are described. The new glucocalixarene bolaamphiphile destabilizes bilayers of saturated lipids whereas it rigidifies those of unsaturated lipids, thus reducing leakage of calcein from the liposome internal aqueous compartment. Moreover, from fluorescence and turbidimetry experiments it was found that the glucose units of bolaamphiphile 1 functionalised liposomes allow a specific multivalent interaction with the tetrameric glucose binding protein Concanavalin A. These results therefore represent a novel strategy to functionalise liposomes with saccharides, exploiting multivalent glycosylated ligands to be used in the preparation of drug delivery systems potentially able to target specific lectins.

Calixarene-based multivalent ligands.

Multivalency is a powerful concept which explains the strong binding observed in biological systems and guides the design and synthesis of ligands for self-assembly and molecular recognition in Chemistry. The phenol-formaldehyde cyclic oligomers, called calixarenes, have been used as scaffolds for the synthesis of multivalent ligands thanks to the fact that they have a variable number of reactive positions for attaching the ligating functions, well defined conformational properties and, in some cases, cavities of molecular dimensions eventually able to encapsulate guest species. This tutorial review illustrates the fundamental aspects of multivalency and the properties of calixarene-based multivalent ligands in lectin binding and inhibition, DNA condensation and cell transfection, protein surface recognition, self-assembly, crystal engineering, and nanofabrication.

New efficient calixarene amide ionophores for the selective removal of strontium ion from nuclear waste: synthesis, complexation, and extraction properties.

Three novel lower rim hexamide derivatives 5(6), 7(6), and 9(6) of p-hydroxycalix[6]arene and four octamides 5(8), 7(8)-9(8) derived from the corresponding p-hydroxycalix[8]arene were synthesized, and their potential as extractants in radioactive waste treatment was evaluated, in comparison with upper rim analogues 12(6) and 12(8) and other existing selective neutral ionophores currently used in radioactive waste treatment. Extraction of alkali and alkaline earth metal picrates from water to dichloromethane, and of the corresponding nitrates from acidic water solution simulating radioactive waste, to 2-nitrophenyl hexyl ether (NPHE), showed that the lower rim amides extract divalent cations much better than monovalent ones. The upper rim hexa-12(6) and octamide 12(8) are very inefficient ligands, hardly extracting any cation. In all cases, p-alkoxy octamides are more efficient and selective extractants than the corresponding hexamides. In the case of simulated waste solutions, the distribution coefficients for strontium removal by octamides (6.5 < D(Sr) < 30) are much higher than the corresponding value (D(Sr)) found for dicyclohexyl-18-crown-6 (DC18C6), and the same applies for the strontium/sodium selectivity, which is 6500 < D(Sr)/D(Na) < 30 000 for octamides and 47 for DC18C6. ESI-MS, UV-vis, and X-ray crystal structure studies give consistent results and indicate the formation of 2:1 (cation/ligand) strontium complexes for all octamides tested. Stability constants were determined in homogeneous methanol solution for alkali metal (log beta(11) < or = 2), calcium (4.3 < or = log beta(11) < or = 6.0; 9.4 < or = log beta(21) < or = 12.0), and strontium (5.6 < or = log beta(11) < or = 12.3) ions using a UV-vis competition method with 1-(2-pyridylazo)-2-naphthol (PAN). They confirm the high efficiency and high divalent/monovalent selectivity found in metal ion extraction experiments for the new octamide ligands. Evidence for a positive cooperative effect between the two metal ion binding sites was obtained in the case of the Ca(2+) complex of octamide 1(8).

Catalysis of acyl group transfer by a double-displacement mechanism: the cleavage of aryl esters catalyzed by calixcrown-Ba2+ complexes

The scope of the barium salt of p-tert-butylcalix[4]arene-crown-5 as a transacylation catalyst has been defined by evaluating its efficiency in the methanolysis of a series of aryl acetates at 25.0 degrees C in MeCN/MeOH 9:1 (v/v) under slightly basic conditions. In this system a phenolic hydroxyl is the acyl-receiving and -releasing unit in a double-displacement mechanism. The complexed barium ion acts both as a nucleophile carrier and a built-in Lewis acid in providing electrophilic assistance to the ester carbonyl both in the acylation and deacylation step (nucleophilic-electrophilic catalysis). Turnover capability is ensured by the acylated intermediate reacting with the solvent more rapidly than the original ester, but a serious drawback derives from the incursion of back-acylation of the liberated phenol. A gradual shift from rate-determining deacylation (p-nitrophenyl acetate) to rate-determining acylation (phenyl acetate) is observed along the investigated series. It is shown that the scope of the catalyst is restricted to acetate esters whose reactivity lies in the range approximately defined by the phenyl acetate-p-nitrophenyl acetate pair, with a maximum efficiency for p-chlorophenyl acetate. Moreover, the catalyst effectively promotes ester interchange between phenols, showing that its activity is not limited to solvolysis reactions. The very high sensitivity of the rate of acylation of the catalyst to leaving group basicity has been interpreted as due to rate-determining decomposition of the tetrahedral intermediate, which is believed to arise from the presumably low basicity of the metal ion stabilized nucleophile. The turnover frequency was in the range of 3.8 x 10(-4) min(-1) for phenyl acetate to 7.4 x 10(-3) min(-1) for p-nitrophenyl acetate ([ArOAc]0=4.0 mM]). A first attempt to enhance the rate of acylation of the catalyst through intramolecular general acid catalysis is also described.

2,2'-bipyridine lariat calixcrowns: a new class of encapsulating ligands forming highly luminescent Eu3+ and Tb3+ complexes

A new class of calix[4]arene crown ethers with one or two bipyridines appended to the polyether ring (lariat calixcrowns) have been designed and synthesized; the luminescence properties of their Eu3+ and Tb3+ complexes have been studied in acetonitrile. In this solvent, long lifetimes for the metal emitting states and high metal-luminescence intensities obtained upon ligand excitation have been observed in both Eu3+ and Tb3+ complexes. The association constants in methanol have been determined for some of the complexes studied.

Recognition of cationic species with synthetic receptors.

In the past year progress in the study of cationic species has been made, particularly in our understanding of the factors which control the selective recognition of biologically important cations such as ammonium, alkali and alkaline earth metal ions, and of metal ions used in biomedicine such as lanthanides and iron(III). Based on this knowledge, several new hosts with improved transport, photophysical and biological properties have been designed.