Crystal Surface Reactivity of Esterase@Zeolitic Imidazolate Framework Biocomposites

TL;DR

This paper explores how combining esterase with ZIF materials enhances enzyme activity and biocompatibility for decontamination and medical applications.

Contribution

The study introduces a novel biocomposite that synergistically enhances esterase activity and ZIF surface reactivity through biomineralization.

Findings

Esterase@ZIF biocomposites show enhanced hydrolytic activity due to stabilized enzyme conformation and ZIF surface reactivity.

The released imidazole moieties from ZIF promote reactivation of DIFP-inhibited acetylcholinesterase.

Esterase@ZIF exhibits increased biocompatibility compared to pristine ZIF materials in in vitro assays.

Abstract

Esterase@zeolitic imidazolate framework (Esterase@ZIF)
biocomposites
have been synthesized by biomineralization of pig liver esterase to
explore the synergistic interplay between esterase and the ZIF framework
on crystal surface reactivity and biocompatibility. The targeted Esterase@ZIF
crystal phases cover a wide range of ZIF topologies, namely, Zn­(mIm)2 (ZIF-8, 3D sodalite, microporous, mImH = 2-methylimidazole),
Zn­(mIm)2·(mImH)0.5 (ZIF-L, 2D layered,
nonporous), and Zn­(mIm)­(CO3)0.5 (ZIF-C, 3D,
nonporous). As model reactions, we have assessed the hydrolytic decontamination
of the G-type nerve agent simulant diisopropylfluorophosphate (DIFP)
and esterase activity toward indoxyl acetate hydrolysis. The results
show a clear synergistic interplay between esterase and the ZIF framework,
which is attributed to the stabilized open-lid conformation of esterase
and the reactivity of the ZIF crystal surface, leading to enhanced
hydrolytic activity. P–F bond hydrolysis also induces Esterase@ZIF
crystal surface degradation releasing mImH and Zn2+ ions.
Released imidazole moieties enable a nucleophilic attack to DIFP-inhibited
acetylcholinesterase (DIFP@AChE), promoting AChE reactivation and
thereby reversing organophosphorous poisoning. In vitro cytotoxicity
assays toward human neuroblastoma cell lines are indicative of increased
biocompatibility of Esterase@ZIF in comparison to pristine ZIF materials.
These results also exemplify that biomineralization can be used not
only to protect enzymes from harsh environments but to modulate crystal
surface reactivity and biocompatibility.

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