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
Departamento de Química Inorgánica, Universidad de Granada, Av. Fuentenueva S/N, 18071 Granada, Spain.
Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell'Insubria, Via Valleggio 11, 22100 Como, Italy.
ACS Appl Mater Interfaces. 2022 Jun 2;14(23):26501-6. 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 [((-butylCpZr)(OH)O)L]Cl (; L = benzene-1,4-dicarboxylate, -butylCp = -butylcyclopentadienyl, , 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 host-guest assemblies feature a sustained delivery of 2-PAM under simulated biological conditions, with a concomitant reactivation of DIFP-inhibited AChE. Finally, systems have been incorporated into biocompatible phosphatidylcholine liposomes with the resulting assemblies being non-neurotoxic, as proven using neuroblastoma cell viability assays.
有机磷酸酯类神经毒剂和杀虫剂是剧毒化合物，因为它们会导致乙酰胆碱酯酶（AChE）抑制并伴随神经系统损伤。在此，我们报告了用于有机磷酸酯中毒治疗的锆基金属有机多面体（Zr-MOPs）的合成、结构表征及概念验证效用。结果表明形成了坚固的四面体笼状物[((-丁基环戊二烯基锆)(OH)O)L]Cl（；L = 苯-1,4-二羧酸酯，-丁基环戊二烯基 = -丁基环戊二烯基，，且L = 4,4'-联苯二羧酸酯），其装饰有亲脂性烷基残基，并且分别具有内径约为9.8 Å和10.7 Å的可及空腔。这些体系既能捕获有机磷酸酯模型化合物二异丙基氟磷酸酯（DIFP），又能容纳并释放AChE复活剂药物解磷定（2-PAM）。所得的主客体组装体在模拟生物条件下具有2-PAM的持续递送，并伴随DIFP抑制的AChE的复活。最后，这些体系已被整合到生物相容性磷脂酰胆碱脂质体中，所得组装体经神经母细胞瘤细胞活力测定证明无神经毒性。
