A phenazine-linked π-conjugated covalent organic framework for conjugation-driven drug loading.

The rational design of π-conjugated covalent organic frameworks (COFs) represents a promising frontier in functional porous materials for drug delivery, particularly when conjugation-affinity correlations can be harnessed. Herein, we report the synthesis and characterization of a structurally unique phenazine-linked π-conjugated COF (TU-32) constructed from 2,7-di-tert-butylpyrene-4,5,9,10-tetraone and 9,10-dihydro-9,10-[1,2]benzenoanthracene-2,3,6,7,14,15-hexaamine hexahydrochloride. In contrast to conventional 2D COFs that exhibit π-π stacking, this COF adopts an atypical AB stacking mode along the c-axis, resulting in suppressed interlayer π-stacking and enhanced structural regularity. The incorporation of extended π-conjugation through phenazine linkages enables selective interactions with conjugated drug molecules. Among three drug molecules tested-5-fluorouracil, isoniazid, and captopril-the COF demonstrated the highest loading capacity (56 wt%) for 5-fluorouracil, which features a fully conjugated pyrimidine-like ring, followed by isoniazid (54 wt%), which contains a moderately conjugated pyridyl moiety. In contrast, captopril, which lacks significant π-conjugation, showed a lower loading (36 wt%). Our findings underscore the importance of molecular-level π-π interactions in drug encapsulation and highlight how precise framework engineering via π-conjugated building blocks enables conjugation-driven guest affinity, offering key insights and a design blueprint for next-generation conjugated porous frameworks for precision therapeutic delivery.