Reversible Redox Controlled DNA Condensation by a Simple Noncanonical Dicationic Diphenylalanine Derivative

We report the reversible redox-controlled DNA condensation using a simple dicationic diphenylalanine derivative which contains a disulfide unit as linker. Despite the conventional belief that DNA condensing agents require a charge of +3 or higher, this dicationic molecule functions below its critical aggregation concentration, representing a non-canonical DNA condensing agent. The interaction with DNA of the studied compound combines electrostatic effects with hydrophobic/stacking interactions provided with the diphenylalanine moiety. Upon reduction, the condensing agent is cleaved, weakening its interaction with DNA and resulting in DNA decondensation. Oxidation reverses this process, restoring the condensed state. This behavior was confirmed through ThT displacement, circular dichroism, ¹H NMR, and dynamic light scattering studies. Overall, this study introduces an innovative alternative for dynamic DNA manipulation applications.