Pyridinium amphiphiles, abbreviated as SAINT, are highly efficient vectors for delivery of DNA into cells. Within a group of structurally related compounds that differ in transfection capacity, we have investigated the role of the shape and structure of the pyridinium molecule on the stability of bilayers formed from a given SAINT and dioleoylphosphatidylethanolamine (DOPE) and on the polymorphism of SAINT/DOPE-DNA complexes. Using electron microscopy and small angle x-ray scattering, a relationship was established between the structure, stability, and morphology of the lipoplexes and their transfection efficiency. The structure with the lowest ratio of the cross-sectional area occupied by polar over hydrophobic domains (SAINT-2) formed the most unstable bilayers when mixed with DOPE and tended to convert into the hexagonal structure. In SAINT-2-containing lipoplexes, a hexagonal topology was apparent, provided that DOPE was present and complex assembly occurred in 150 mM NaCl. If not, a lamellar phase was obtained, as for lipoplexes prepared from geometrically more balanced SAINT structures. The hexagonal topology strongly promotes transfection efficiency, whereas a strongly reduced activity is seen for complexes displaying the lamellar topology. We conclude that in the DOPE-containing complexes the molecular shape and the nonbilayer preferences of the cationic lipid control the topology of the lipoplex and thereby the transfection efficiency.

Calix[4]arenes diametrically substituted at the upper rim with two melamine units spontaneously form welldefined box-like assemblies in the presence of two equivalents of 5,5-diethylbarbituric acid. These assemblies, consisting of nine different components, are held together by 36 hydrogen bonds and are stable in apolar solvents at concentrations of up to 1 0 -4 M . This paper reports the first X-ray crystal structure, and the MALDI TOF mass spectra together with the complete 'H NMR spectroscopic characterization of these hydrogen-bonded assemblies. The crystal structure clearly shows that the assemblies are stereogenic, as a result of the antiparallel orientation of the two rosette motifs. Furthermore, the synthesis of twelve new l ,3-bis(melamine)calix[4]arenes carrying different numbers and types of functionalities at the upper rim is described. Detailed 'HNMR spectroscopic studies on the as-

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Several geminal bis-urea compounds were synthesised by means of an acid-catalysed condensation of various benzaldehydes with different monoalkylureas. Many of these compounds form thermoreversible gels with a number of organic solvents at very low concentrations (< 3 mm) and which are stable to temperatures higher than 100 8C. Electron microscopy revealed a three-dimensional (3D) network of intertwined fibres, which are several tens of micrometers long and have a width ranging from approximately 30 to 300 nm. The possible aggregate forms and aggregate symmetries were evaluated by means of molecular mechanics calculations. 1 H NMR, 2D NMR, 13 C NMR and 13 C-CP/MAS NMR techniques were used to obtain information about the aggregation and possible aggregate symmetry of geminal bis-ureas in solution, in the gel state, and in the solid state.

The results of a systematic study of the structural isomerism in more than 30 noncovalent hydrogenbonded assemblies are described. These dynamic assemblies, composed of three calix[4]arene dimelamines and six barbiturates/cyanurates, can be present in three isomeric forms with either D 3 , C 3h , or C s symmetry. The isomeric distribution can be readily determined via a combination of 1 H NMR and 13 C NMR spectroscopy. In one case it is shown that the covalent capture of the dynamic assemblies via a ring-closing metathesis (RCM) reaction provides a novel analytical tool to distinguish between the D 3 and C 3h isomeric forms of the assembly. For the D 3 isomer the RCM results in the formation of a cyclic trimer, comprising three dimelamines, whereas for the C 3h isomer a cyclic monomer is formed. Molecular dynamics simulations in chloroform are qualitatively in agreement with the experimental data and reveal that the isomeric distribution is determined by a combination of steric, electronic, and solvation effects. A wide range of isomeric distributions covering all extremes has been found for the studied assemblies. Those with 5,5-disubstituted barbituric acid derivatives exclusively form the D 3 isomer, because steric hindrance between the barbiturate substituents prevents formation of the C 3h and C s isomers. In contrast, assemblies with isocyanuric acid derivatives exhibit increased stability of the C 3h and C s isomers upon increasing the size of the isocyanurate substituent. The outcome of the assembly process can be controlled to a large extent via chiral substituents in the calix[4]arene dimelamines, due to the preferred orientation of the chiral centers.