Molecular-level imaging of hydrogen-bonded organic frameworks by cryogenic low-dose electron microscopy

The fundamental problems associated with structural inhomogeneities of hydrogen-bonded organic frameworks (HOFs), such as surface terminations and host-guest heterostructures that govern their functionalities and growth mechanisms, remain a critical gap in knowledge. This arises from the lack of advanced real-space structural characterization tools with molecular precision. By leveraging state-of-the-art cryogenic low-dose electron microscopy, this work overcomes the beam damage limitations of traditional techniques and elucidates the crystal structures, surface terminations, and host-guest structures of HOFs at molecular-level. Real-space observations confirm lateral crystal growth consistent with the terrace-ledge-kink (TLK) model, but deviate from the classical monomer-addition mechanism. Instead, we propose a nonclassical cooperative multisite monomer-addition mechanism, where simultaneous monomer addition at both framework and guest sites eventually drives crystal faceting. • Cryogenic low-dose electron microscopy enables molecular-level imaging of fragile HOF crystals. • Real-space visualization reveals a TLK growth mode driven by weak hydrogen bonding. • A nonclassical cooperative multisite monomer-addition mechanism governs crystal faceting. • The methodology establishes a generalizable paradigm for structural studies of HOF systems.