Non-covalent synthesis of organic nanostructures

This review describes the synthesis, characterization and functionalization of hydrogen bonded, box-like assemblies. These assemblies are formed upon mixing bismelamine calix[4]arenes with a complementary barbiturate in apolar solvents. Various techniques for the characterization have been used, like 'H NMR spectroscopy, X-ray crystallography and a novel MALDI-TOF MS technique. The use of cyanurates instead of barbiturates results in the formation of three conformational isomers. The ratio in which these assemblies are formed depends on the N-substituent of the cyanurate. Substituting the bismelamine calix[4]arenes with a variety of functional groups enables the formation of assemblies in which functionalities are gathered around a box-like cavity. Mixing these homomeric assemblies creates a dynamic combinatorial library of heteromeric assemblies. INTRODUCTION During the last decade self-assembly has emerged as a tool that enables relatively easy access to molecular assemblies of high molecular weight and nanoscopic dimensions'. The elegance of selfassembly lies in the fact that the extent of covalent synthesis is reduced to the level of the individual components or modules, that contain information necessary for the formation of the assembly. Like Nature, chemists employ noncovalent, reversible interactions for the recognition of the modules, for instance hydrogen bonding2 or metal-ligand interactions3. The advantage of using this kind of reversible interactions over irreversible covalent interactions is that it allows for 'self-correction' since the assembly is at thermodynamic equilibrium. A large variety of assemblies based on noncovalent interactions has been reported over the past decade illustrating how the concept of self-assembly has triggered the creativity of chemists4. One of our recent activities concerns the development of artificial receptors using a modular approach. Hitherto we have focused on covalent structures, based on a combination of modules like caljx[4]arenes, resorcin[4]arenes and cycl~dextrins~. With the synthesis of the holand, comprising two calix[4]arenes and two resorcin[4]arenes, we have reached the boundaries of synthetically accessible receptor molecules6. To eliminate the elaborate syntheses and to create more flexibility in the receptor molecules we recently started a research program that should lead us towards functional self-assembled aggregates. Here we describe our recent achievements so far in this area. SYNTHESIS AND CHARACTERIZATION OF HYDROGEN BONDED BOX-LIKE ASSEMBLIES Complementary hydrogen bonding between cyanuric acid and melamine has received considerable attention as a structural motif for self-assembly. Work from the groups of Whitesides7 and Lehn' has shown that the recognition between these components can be used to form different types of aggregates, either lineair or crinkled tapes, or cyclic rosettes. Which type of aggregate is formed critically depends on the extent of preorganization of the complementary binding units and on steric interactions between their substituents. Due to the facile synthesis and the high degree of controllability we have decided to use this recognition motif for the self-assembly of hydrogen bonded box-like assemblie8 lo. 'Plenary lecture presented at the 12th International Conference on Organic Synthesis, Venice, 28 June-2 July 1998. Other presentations are published in this issue, pp. 1449-1512.