Synthesis, Characterization, Self-assembling and Encapsulation Properties of Hyperbranched Hydrophobic Dendritic Amphiphiles

This thesis described the synthesis, self-assembling and/or encapsulation properties of two different classes of amphiphilic dendritic compounds. The first set of amphiphilic dendrons [Gn]-OEG8 128--130 (n = 1--3) are dendritic-linear hybrid molecules that have a hydrophobic hydrocarbon (HC) dendron connected to a hydrophilic octa(ethylene glycol) chain. The effect of the branching architecture on their self-assembling properties was then compared to that of their doubly branched [Dn]-OEG8 and linear [Ln]-OEG8 analogs, which were also prepared in this study. The second set of compounds are a series of amphiphilic dendrimers OEG-[Gn]-dendrimer 171--173 (n = 0--2) decorated with surface tetra(ethylene glycol) chains on the periphery of a HC dendrimer. The size effect of the HC sector on their self-assembling and drug encapsulation properties with indomethacin was examined.;The structures of all compounds were characterized by 1H and 13C NMR spectroscopy, mass spectrometry, and gel permeation chromatography. Their self-assembling and host-guest complexation properties, such as critical micellar/association concentrations (CMC/CAC), micro-environmental polarity, particle size distributions and drug loading capacity were investigated by various physical techniques such as UV and fluorescent spectroscopy, as well as static and dynamic laser light scattering. Based on our experimental findings, we were able to confirm the results obtained from earlier theoretical simulations. First, for both series of dendritic amphiphiles, their CMC/CAC values decreased with increasing size of the hydrophobic segment. Second, with the same molecular formula and hydrophobic/lipophilic balance (HLB), amphiphiles containing a hydrophobic segment of a higher branching degree possessed a higher CMC/CAC value. Third, the micellar core of amphiphiles with a dendritic hydrophobic sector was more polar than that of non-dendritic amphiphiles having the same molecular formula. Fourth, the micellar core of a dendritic amphiphile of a higher generation was more non-polar than that of the lower generation analogues. All the findings could be correlated to the size (i.e. length or generation) and the architecture (i.e. branching pattern) of the hydrophobic HC sector.;Three unusual findings that deviated from previous theoretical simulations were noted. First, the doubly branched [D2]-OEG8 132 was found to have a lower CMC value than the linear [L2]-OEG8 134. This anomaly could be rectified if backfolding of the linear HC chain is taken into consideration. Second, based on DLS study, it was noted that the 'unimolecular' OEG-[Gn]-dendrimers 171--173 were capable of forming 'giant' aggregates in aqueous solutions. Third, their drug loading capacity did not correlate to the size of the hydrophobic HC sector. The latter two findings revealed the complexity in dealing with the understanding of the self assembling and host-guest complexation processes of these large amphiphile dendrimers. Prior to our work, only theoretical calculations had been carried out. The work described in this thesis serves to provide solid experimental evidence in support of the theoretical simulations and offer additional insights that were previously neglected in this subject area.