Reversible Sequence-Dependent DNA Coacervation with an Azobenzene Intercalator

Based on electrostatic interactions and entropic gains from counterion release, DNA coacervates constitute an exciting example of associative assemblies due to high local DNA concentrations and their applications in therapeutics, biomimicry, and biosensing. Because charge density is not affected by DNA sequence, resulting coacervates are intrinsically nonspecific to the nucleobase composition of DNA. Here, we report that using an azobenzene-based DNA binder, AzodiGua, able to intercalate between DNA base pairs, can bring sequence sensitivity to DNA coacervation. We show that different amounts of AzodiGua are necessary to induce coacervation as a function of the double- or single-stranded nature of DNA, the fraction and distribution of GC base pairs a per double-stranded DNA oligonucleotides. In addition, resulting coacervates are shown to be reversibly photosensitive via <i>trans</i>/<i>cis</i> isomerization of AzodiGua's azobenzene moiety. Due to the lower efficiency of the <i>cis</i>-isomer for DNA coacervation, coacervates can be dissolved by UV illumination and reformed back by blue light illumination. Interestingly, selective sequestration of the <i>trans</i>-AzodiGua by α-cyclodextrin allows us to achieve a reversed-photocontrol regime, under which coacervates are favored under UV illumination.