Crystalline mate strategy for berberine hydrochloride: solvent-polarity-tuned co-crystallization

Single-crystal X-ray diffraction is one of the most reliable techniques for elucidating the molecular structures, while it requires high-quality single crystals. The crystalline mate (CM) strategy has recently emerged as an effective method to induce rapid and selective co-crystallization. Here, we demonstrate that this strategy can be reliably extended to ionic systems using the neutral trinuclear silver pyrazolate complex Ag 3 Pz 3 as a crystallization mate. By regulating solvent polarity, two co-crystals of silver pyrazolate berberine hydrochloride Ag 3 Pz 3 ·BCl, SF (sandwich form) and NSF (non-sandwiched form), were obtained. In SF , neutral Ag 3 Pz 3 simultaneously engages the Cl − anion via π-acid/base contacts and the berberine cation through weak Ag...O coordination. Remarkably, SF can also be crystallized directly from crude Coptis chinensis extract without prior purification. In NSF , due to the influence from methanol or ethanol, Ag 3 Pz 3 rearranges into a rare anionic Ag 3 Pz 4 cluster that serves as the counterion to berberine. These results establish solvent polarity as a decisive factor governing CM-mediated co-crystal assembly and broaden the applicability of the crystalline-mate concept to ionic systems.