Hydration control in molecular salts through counterion selection

Abstract Predicting when and why molecular salts form hydrates has remained a significant problem in solid-state chemistry, despite its impact on the stability and performance of industrially relevant materials. Here, we identify counterion charge localization as a key determinant of hydrate formation in molecular salts, providing a framework for predicting and controlling solid-state hydration. By analyzing over 31,000 crystal structures and performing electron density calculations, we show that delocalized counterion charge suppresses hydrate formation, while localized charge promotes it. This principle makes hydration propensity a more tuneable property (from ~80% to <10%) through considered counterion selection. Guided by these insights and the Δp K a rule, we experimentally demonstrate rational control of hydration in salts of 4-aminoacetanilide. Our results establish a direct link between molecular electrostatics and crystallization outcomes, affording predictive design of molecular salts with tailored hydration behavior.