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Introducing these interactions into reticular materials offers a new approach to constructing artificial enzymes and more closely mimicking the catalytic microenvironment. Herein, a pair of chiral hydrogen\u2010bonded organic frameworks (LHOF and DHOF) has been constructed, and their unique crystal structures have been determined. These porous chiral HOFs act as substrate enrichment pockets, active cavities, and possess aldolase\u2010like activity, which can catalyze the asymmetric synthesis of the enantiomeric bioactive molecule, 3\u2010hydroxy\u20101,5\u2010diphenyl\u20101\u2010pehtanone. Compared to the right\u2010handed enantiomer, the left\u2010handed compound shows superior reactive oxygen species (ROS) scavenging capability in an LPS\u2010induced inflammatory model. Further studies demonstrate that the anti\u2010neuroinflammatory effect of this chiral product can reverse microglia phenotype, thereby enhancing their A\u03b2 phagocytosis and alleviating Alzheimer's disease symptoms in the 3\u00d7Tg\u2010AD mouse model. Thus, introduction of non\u2010covalent interactions into reticular materials enhances enzyme\u2010mimicking technology and offers new insights into enantioselective in vivo catalysis. This work provides a new paradigm for developing bioinspired materials chemistry and exploring their applications in enantioselective biomimetic catalysis.<\/jats:p>","DOI":"10.1002\/anie.4720702","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:58:15Z","timestamp":1772989095000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chiral Supramolecular Hydrogen Bonding Networks for Enantio\u2010Selective Catalysis Against Neuroinflammation"],"prefix":"10.1002","volume":"65","author":[{"given":"Congcong","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun Jilin P.R. China"},{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei Anhui P.R. 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