Solvent-Directed Phase Control in Disulfide-Linked Metal–Organic Frameworks Revealed by Microcrystal Electron Diffraction

Abstract Precise control over phase, topology, and reactivity in metal–organic frameworks (MOFs) is critical for translating chemical responsiveness into predictable function. Disulfide-linked coordination networks are attractive flexible materials, yet their strong sensitivity to synthesis conditions has hindered mechanistic understanding of how the structure governs reactivity. Here, we achieve phase control in a zinc disulfide MOF system by tuning solvent coordination and water activity, enabling access to a microcrystalline open-pore structure (Zn-MOF-α) and a dense, topologically distinct isomer (Zn-MOF-β) from the same disulfide linker. Microcrystal electron diffraction (MicroED) studies determined both structures directly from micro- and nanocrystalline particles, revealing distinct secondary building units (SBUs), connectivity, and pore architecture. Systematic solvent studies identify water as a driver of α → β transformation, while the reverse transformation (β → α) is accessible in solutions of N,N-dimethylformamide in water (DMF/H2O). Time-resolved experiments reveal a clear time and solvent dependence between the α- and β-phases, supporting distinct assembly pathways. By correlating topology, morphology, Brunauer–Emmett–Teller (BET), thermal gravimetric analysis (TGA), and spectroscopic signatures including electron paramagnetic resonance (EPR), we show that the open α-framework provides higher sulfur-centered radical populations and lower thermal robustness relative to the dense β-phase. Together, these results provide design rules for predictable phase outcomes and topology-dependent disulfide activation in flexible MOFs, enabling rational control of structure–function relationships in responsive porous materials.