Zirconium Metal−Organic Polyhedra with Dual Behavior for Organophosphate Poisoning Treatment
Metadatos
Mostrar el registro completo del ítemAutor
Delgado López, Pedro José; Martín Romera, Javier David; Perona, Cristina; Vismara, Rebecca; Rodríguez Maldonado, Carmen; Carmona Fernández, Francisco Jesús; Rodríguez Navarro, Jorge AndrésEditorial
American Chemical Society
Materia
Nerve agents Host-guest chemistry Pesticide Controlled drug delivery Metal-organic cages
Fecha
2022-06-02Referencia bibliográfica
ACS Appl. Mater. Interfaces 2022, 14, 26501−26506. [https://doi.org/10.1021/acsami.2c06025]
Patrocinador
Spanish MCIN/AEI PID2020-113608RB-I00; FEDER/Junta de Andalucia-Conserjeria de Economia y Conocimiento B-FQM-364-UGR18 B-FQM-006-UGR18; FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades P18-RT-612 P20_00672; Fondazione CRUI; programa Juan de la Cierva Formacion; Spanish Government PID2020-118117RB-I00; Center for Forestry Research & Experimentation (CIEF); European Commission SEJIGENT/2021/059 PROMETEU/2021/054; La Caixa Foundation 100010434 LCF/BQ/PR20/11770014; "Maria de Maeztu" Program for Centers of Excellence in RD CEX2019-000919-M; H2020-MSCA-IF2019-888972-PSust-MOFResumen
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.