LAUSR

Heterofunctional dendrimers with internal and external representation of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over structure, molecular weight, number and location of different cargo across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose character are the pinnacle of precision polymers and thereof are highly attractive by the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which lead to inherent limitation for their full potential use as precision carriers. Consequently, we here embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a Proof-of-Concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) were successfully accomplished by the elegant and simple design of AB2C monomers, amalgamated from two traditional AB2 monomers. By utilizing Fluoride-Promoted Esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day reaction time, with a molecular weight of 15 kDa and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of post-functionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes and PEG chains is achieved, as well as crosslinking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles or biomolecules.