Design, synthesis, and characterization of triazaadamantane based monomers and dendrimers.

摘要

This thesis describes the progress towards developing a pH dependent, degradable dendrimer consisting of 2,4,6-triaryl-1,3,5-triazaadamantane units. A 7-hydroxymethyl-2,4,6-triphenyl-1,3,5-triazaadamantane subunit was synthesized and its structural properties were examined by computational studies, 1H NMR experiments, and X-ray analysis. The major isomer was concluded to exist with two equatorial phenyl rings and one axial phenyl ring relative to the [1,3,5]triazinane ring. By varying the electronic properties on the phenyl ring, the hydrolysis rate of triazaadamantane degradation can be tuned as observed by UV/Vis studies. Possible triazaadamantane condensation and hydrolysis mechanisms based on thermodynamic arguments are also presented.; Furthermore, the synthesis of triazaadamantane based dendrimers is described. These dendrimers contain a hydrophobic core and three triazaadamantane units. Polyethylene glycol chains were located on the periphery of the macromolecule to impart solubility in aqueous environments. UV/Vis and fluorescence studies suggest that the dendrimer can encapsulate small molecules such as 1-anilino-8-sulfonic acid and Rose Bengal. Preliminary cyctotoxicity studies employing the XTT assay on MDA-MB-231 human breast cancer cells indicated that the dendrimers were not cytotoxic.; These triazaadamantane macromolecules may find broad application as drug carriers and for the encapsulation and release of other substances, similar to the Trojan horse strategy. Their ability to act as proton sponges makes them particularly interesting with regards to their potential as artificial gene delivery vectors.