Organophosphate Detoxification and Acetylcholinesterase Reactivation Triggered by Zeolitic Imidazolate Framework Structural Degradation Martín Romera, Javier David Borrego Marin, Emilio Jabalera Ortiz, Pedro J. Carraro, Francesco Falcaro, Paolo Barea Martínez, Elisa María Carmona Fernández, Francisco Jesús Rodríguez Navarro, Jorge Andrés Controlled drug delivery Nerve agent Metal−organic framework Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn−L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P−X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate. P−X hydrolysis is accompanied by ZIF structural degradation (Zn−imidazolate bond hydrolysis), with the concomitant release of the imidazolate linkers and zinc ions representing up to 95% of ZIF particle dissolution. The delivered imidazolate nucleophilic attack on the OP@AChE adduct gives rise to the recovery of AChE enzymatic function. P−X bond breakdown, ZIF structural degradation, and AChE reactivation are dependent on imidazolate linker nucleophilicity, framework topology, and particle size. The best performance is obtained for 20 nm nanoparticles (NPs) of Zn(2-methylimidazolate)2 (sod ZIF-8) exhibiting a DIFP degradation half-life of 2.6 min and full recovery of AChE activity within 1 h. 20 nm sod ZIF-8 NPs are not neurotoxic, as proven by in vitro neuroblastoma cell culture viability tests. 2024-05-15T10:11:51Z 2024-05-15T10:11:51Z 2024-02-12 journal article Javier D. Martin-Romera, Emilio Borrego-Marin, Pedro J. Jabalera-Ortiz, Francesco Carraro, Paolo Falcaro, Elisa Barea, Francisco J. Carmona, and Jorge A. R. Navarro ACS Applied Materials & Interfaces 2024 16 (8), 9900-9907 DOI: 10.1021/acsami.3c18855 https://hdl.handle.net/10481/91814 10.1021/acsami.3c18855 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional American Chemical Society