Conformational Bias and Transmission Drive Structural Differentiation of Covalent Organic Frameworks

During COF crystallization, weak interactions continuously bias the conformational distribution of monomers during crystal nucleation and growth. Conformational evolution and selection typically occur across multiple time and length scales, posing significant challenges for direct observation using current in situ structural techniques. Therefore, it remains unclear how monomer conformational bias is selected, transmitted, and progressively accumulated to yield the final structural differentiation. Here, we proposed a strategy using molecular conformational freedom to synchronize and transmit conformational bias during COF crystallization. Based on this strategy, we successfully achieved structural differentiation in COFs. Notably, building blocks with high conformational freedom exhibited lower torsional barriers, enabling more efficient transmission of stacking information during crystal growth. This led to three stacking isomers, including unidirectional inclined stacking, bidirectional inclined stacking, and alternately bidirectional inclined stacking. These different stacking modes directly regulated the photocatalytic reduction activity. This work not only enabled the controlled synthesis and functional tailoring of COF stacking isomers, but more importantly, proposed a new strategy to regulate the covalent assembly process through conformational selection. This strategy provided a new perspective for understanding conformational selection in COF crystallization and for designing complex framework materials.