Organophosphate Detoxification and Acetylcholinesterase Reactivation Triggered by Zeolitic Imidazolate Framework Structural Degradation
Metadatos
Mostrar el registro completo del ítemAutor
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 AndrésEditorial
American Chemical Society
Materia
Controlled drug delivery Nerve agent Metal−organic framework
Fecha
2024-02-12Referencia bibliográfica
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
Patrocinador
Spanish MCIN/AEI/10.13039/501100011033 (project PID2020-113608RB-I00; TED2021-129886B-C41); NATO Science for Peace and Security Programme under grant no. G5889-“SARS-CoV-2 Multi-Messenger Monitoring for Occupational Health & Safety-SARS 3M”; Plan Propio de Investigación-Universidad de Granada for a predoctoral fellowship; FEDER/Junta de Andalucía-Consejería de Economía, Conocimiento, Empresas y Universidad (Project C-EXP-056-UGR23); Universidad de Granada for covering the Open Access Article Publication ChargeResumen
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.