Zirconium Metal–Organic Polyhedra with Dual Behavior for Organophosphate Poisoning Treatment

• Published in: ACS applied materials & interfaces 2022-06, Vol.14 (23), p.26501-26506
• Main Authors: Delgado, Pedro, Martin-Romera, Javier D., Perona, Cristina, Vismara, Rebecca, Galli, Simona, Maldonado, Carmen R., Carmona, Francisco J., Padial, Natalia M., Navarro, Jorge A. R.
• Format: Article
• Language: English
• Subjects: Biological and Medical Applications of Materials and Interfaces
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.2c06025

Organophosphate nerve agents and pesticides are extremely toxic compounds because they result in acetylcholinesterase (AChE) inhibition and concomitant nerve system damage. Herein, we report the synthesis, structural characterization, and proof-of-concept utility of zirconium metal–organic polyhedra (Zr-MOPs) for organophosphate poisoning treatment. The results show the formation of robust tetrahedral cages [((n-butylCpZr)3(OH)3O)4L6]­Cl6 (Zr-MOP-1; L = benzene-1,4-dicarboxylate, n-butylCp = n-butylcyclopentadienyl, Zr-MOP-10, and L = 4,4′-biphenyldicarboxylate) decorated with lipophilic alkyl residues and possessing accessible cavities of ∼9.8 and ∼10.7 Å inner diameters, respectively. These systems are able to both capture the organophosphate model compound diisopropylfluorophosphate (DIFP) and host and release the AChE reactivator drug pralidoxime (2-PAM). The resulting 2-PAM@Zr-MOP-1­(0) host–guest assemblies feature a sustained delivery of 2-PAM under simulated biological conditions, with a concomitant reactivation of DIFP-inhibited AChE. Finally, 2-PAM@Zr-MOP systems have been incorporated into biocompatible phosphatidylcholine liposomes with the resulting assemblies being non-neurotoxic, as proven using neuroblastoma cell viability assays.