Polyimidazolium amphiphilic dendrimers on thiacalix[4]arene and gallic acid platforms via copper-free click chemistry: synthesis, self-assembly and DNA binding

Abstract

A divergent synthetic scheme based on copper-free click chemistry was used to obtain two types of bromine-containing dendrimers with a thiacalix[4]arene or gallic acid core. These dendrimers were then terminated with cationic imidazolium groups via the Menshutkin reaction to obtain a series of amphiphilic dendrimers. The critical aggregation concentrations of the dendrimers were determined using three different probes. It was demonstrated that the solubilization capacity with respect to the hydrophobic Orange OT substrate logically increases with the transition from the second to the third generation, whereas the first generation does not solubilize the dye. In the case of the thiacalix[4]arene core, the most compact aggregates (approximately 80 nm) were obtained in the second generation. In the case of gallic acid, the most compact aggregates (approximately 30 nm) were obtained in the second and third generations, with the third generation forming the most monodisperse particles. Steady-state and time-resolved fluorescence spectroscopy revealed that the third generation on both the gallic acid and thiacalix[4]arene platforms interacts most effectively with calf thymus DNA, displacing ethidium bromide. The addition of third-generation dendrimers causes DNA compaction, forming particles measuring approximately 70–120 nm, and results in surface recharging to +40 mV. Since the CD data show that the addition of dendrimers results in DNA ordering (transition to the C-form), the obtained second- and third-generation dendrimers are promising as potential matrices for stabilization, storage, or delivery of nucleic acids in future studies.