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 possibility of their applications for drug and gene delivery. Because charge density is not affected by DNA sequence, resulting coacervates are intrinsically non-specific 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 DNA double- or single-stranded nature, as well as of its GC content. In addition, resulting coacervates were shown to be reversibly photosensitive via trans/cis isomerization of AzodiGua’s azobenzene moiety, due to lower efficiency of the cis-isomer for DNA coacervation. The photocontrol could finally be reversed by adding α-cyclodextrin which selectively binds to trans-AzodiGua forming inclusion complex and hinders it from coacervation, without affecting the coacervation efficiency by the cis-isomer. UV-induced trans-to-cis isomerization of AzodiGua thus leads to dissolution of the coacervates in absence of α-cyclodextrin, and to their reformation in presence of α-cyclodextrin.