“Single–Single” Amphiphilic Janus Dendrimers Self-Assemble into Uniform Dendrimersomes with Predictable Size

Abstract

An accelerated modular synthesis of six libraries containing 29 amphiphilic Janus dendrimers, employed to discover and predict functions via primary structures, is reported. These dendrimers were constructed from a single hydrophobic and a single hydrophilic dendron, interconnected with l-Ala to form two constitutional isomeric libraries, with Gly to produce one library, and with l-propanediol ester to generate two additional constitutional isomeric libraries. They are denoted "single-single" amphiphilic Janus dendrimers. Assemblies obtained by injection of their ethanol solution into water were analyzed by dynamic light scattering and cryogenic transmission electron microscopy. A diversity of complex structures including soft and hard dendrimersomes, cubosomes, solid lamellae, and rod-like micelles were obtained in water. It was discovered that the "single-single" amphiphilic Janus dendrimers containing three triethylene glycol groups in the hydrophilic dendron favored the formation of dendrimersomes. Assemblies in bulk analyzed by differential scanning calorimetry and powder X-ray diffraction revealed that the amphiphilic Janus dendrimers with melting point or glass transition below room temperature self-assemble into soft dendrimersomes in water, while those with higher temperature transitions produce hard assemblies. In the range of concentrations where their size distribution is narrow, the diameter of the dendrimersomes is predictable by the d-spacing of their assemblies in bulk. These results suggested the synthesis of Library 6 containing two simpler constitutional isomeric benzyl ester based amphiphilic Janus dendrimers that self-assemble in water into soft dendrimersomes and multidendrimersome dendrimersomes with predictable dimensions.