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

Abstract

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) 3 O) 4 L 6 ]Cl 6 (Zr-MOP-1; L = benzene-1,4dicarboxylate, 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,

Altering the solubility of metal–organic polyhedra via pendant functionalization of Cp3Zr3O(OH)3 nodes

“…18 ZrMOP s with 180° bridging ligands generally form tetrahedral (V 4 L 6 ) architectures as a kinetic product, and lantern (V 2 L 3 ) architectures as a thermodynamic product, though ligand geometry also plays a role. 19,22…”

“…6,18 ZrMOPs have shown promise for applications such as gas separation, small molecule capture, and catalysis. [19][20][21] These cages comprise six-coordinate, trinuclear zirconium nodes (half that of the UiO-66 cluster) with three cyclopentadienyl capping ligands and carboxylate-based bridging ligands. 18 ZrMOPs with 180°bridging ligands generally form tetrahedral (V 4 L 6 ) architectures as a kinetic product, and lantern (V 2 L 3 ) architectures as a thermodynamic product, though ligand geometry also plays a role.…”

“…18 ZrMOPs with 180°bridging ligands generally form tetrahedral (V 4 L 6 ) architectures as a kinetic product, and lantern (V 2 L 3 ) architectures as a thermodynamic product, though ligand geometry also plays a role. 19,22 The most common route to solubilization of ZrMOPs is counterion exchange. 23 The use of zirconocene dichloride as a precursor delivers ZrMOPs with chloride counterions, which can be exchanged post-synthetically with triflates to enhance solubility.…”

“…In fact, only n-butyl pendants have been reported thus far. 19,25 We hypothesized that the cyclopentadienyl ligands could be used as general sites for functionalization to tune the properties of such MOPs. This approach has an advantage in that it doesn't change the organic bridging ligands so that the overall topology and self-assembly should be invariant to the modifications.…”

“…Three new MOPs were then synthesized with nodebased benzyl-, vinylbenzyl-, and trifluoromethylbenzyl-moieties, named ZrMOP-ben, ZrMOP-vb, and ZrMOP-tfmb, respectively. These ZrMOPs were fully characterized through 1 H/ 19 F NMR, high-resolution mass spectrometry, infrared spectroscopy, and single-crystal X-ray diffraction. Subsequently, ICP-mass spectrometry was used to evaluate the effects of ZrMOP node-functionality on solubility.…”