Plasma-driven radical and electrostatic processes bias polymorph selection in mannitol crystallization

Low-temperature plasma is increasingly used to modulate chemical reactions at liquid interfaces, yet how plasma–solution interactions influence molecular assembly and crystallization remains poorly understood. Controlling crystal polymorphs is particularly challenging because metastable phases are often difficult to access reproducibly using conventional solution chemistry. Here, we show that direct exposure of aqueous mannitol solutions to dielectric barrier discharge plasma selectively promotes crystallization of the metastable δ polymorph. Plasma treatment yields δ-form contents approaching 90–95%, whereas charge-only conditions or plasma-treated solvent alone produce only the stable α/β forms, indicating that neither electrostatic charging nor solution chemistry alone explains the transition. Spectroscopic analyses reveal two coupled effects: plasma-generated reactive species induce partial dehydration and dehydrogenative condensation of mannitol, while direct plasma–solute contact introduces transient charge states that perturb intermolecular packing during nucleation. These findings identify plasma as a dual chemical-electrostatic driver that biases crystallization pathways toward otherwise inaccessible polymorphs, establishing a strategy for plasma-assisted crystal engineering.