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 Ag₃Pz₃ as a crystallization mate. By regulating solvent polarity, two co-crystals of silver pyrazolate berberine hydrochloride Ag₃Pz₃·BCl, SF (sandwich form) and NSF (non-sandwiched form), were obtained. In SF, neutral Ag₃Pz₃ 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, Ag₃Pz₃ rearranges into a rare anionic Ag₃Pz₄ 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.