Stepwise noncovalent synthesis leading to dendrimer-based assemblies in water

We provide detailed insight into complex supramolecular assembly processes by fully characterizing a multicomponent model system using dynamic light scattering, cryogenic transmission electron microscopy, atomic force microscopy, and various NMR techniques. First, a preassembly of a host molecule (the fifth-generation urea-adamantyl poly(propylene imine) dendrimer) and 32 guest molecules (a water- and chloroform-soluble ureidoacetic acid guest) was made in chloroform. The association constant in chloroform is concealed by guest self-association and is therefore higher than 103 M-1. Via the neat state the single-host complex was transferred to water, where larger dendrimer-based assemblies were formed. The core of these assemblies, consisting of multiple host molecules (on average three), is kinetically trapped upon dissolution in water, and its size is constant irrespective of the concentration. The guest molecules forming the corona of the assemblies, however, stay dynamic since they are still in rapid exchange on the NMR time scale, as they were in chloroform. A stepwise noncovalent synthesis provides a means to obtain metastable dynamic supramolecular assemblies in water, structures that cannot be formed in one step.