Molecularly Imprinted Porous-Organic Framework with pH-Responsive Adsorption Sites for the Selective Adsorption of Iron

Regulating brain iron metabolism and reducing neuronal ferroptosis is proven to be a potential method for treating Alzheimer's disease (AD). However, gastric juice has a pH of 1.1-2.2 where a large number of interfering ions are dissociated from the food, which in turn causes traditional oral iron chelators to be saturated and inactivated. Herein, poly(4-vinylbenzoic acid) polymer chains were introduced as guided by Fe3+ ion template into the porous network (TpPa-1) via molecularly imprinted technology to obtain porous iron chelators, COOH@TpPa-1. The COOH@TpPa-1 maintains a multiple hydrogen bonding structure to block the channels in the stomach (pH similar to 1.1-2.2) with a strongly acidic environment, so just a small amount of active sites have been occupied. As COOH@TpPa-1 enters the colon, the alkaline environment disrupts the original hydrogen-bonded structure and forms anionic fragments, the bonding affinity for Fe3+ ions was similar to 4.0 times that in the stomach, and also gave a high selective coefficient 4.2 times higher than that of conventional iron chelators. These designable "on" and "off" states promote the effective enrichment of iron ions within the colon by the porous chelator and produce a favorable therapeutic effect on Alzheimer's symptoms caused by ferroptosis in mice.