Toward the Synthesis of Isobutylene-Based Dendrimers for Targeted Drug Delivery

Dendrimers are well-defined, highly branched, and spherical macromolecules of nanometer dimensions. They possess unique properties including uniform size, multivalent surface, precise architecture and internal cavities, which can be functionalized further and make them attractive for biological and drug delivery applications. Isobutylene (IB)-based dendrimers can be an interesting class of drug delivery materials since IB-based polymers are known to be biocompatible and biostable. In our research, we aim to synthesize well-defined IB-based dendrimers by employing enzyme-catalyzed functionalization that could potentially be used for targeted drug delivery to kill cancer cells. In this work, we designed the synthesis of the building blocks of our dendrimer using a modified Mayr method.  Two different tertiary alcohol difunctional initiators in conjunction with TiCl₄ were used to synthesize monodisperse telechelic oligoIBs.  Our results demonstrate that the structure of the initiator has a significant effect on the initiating efficiency.  In a reaction initiated by 2,4-dimethyl-2,4-pentanediol, 47%  initiator efficiency was achieved. In contrast, the 2,6-dihydroxy-2,4,4,6-tetramethylheptane  initiator yielded 94% of initiator efficiency.