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A self-degradable hydrogel sensor for a nerve agent tabun surrogate through a self-propagating cascade.

ABSTRACT: Nerve agents that irreversibly deactivate the enzyme acetylcholinesterase are extremely toxic weapons of mass destruction. Thus, developing methods to detect these lethal agents is important. To create an optical sensor for a surrogate of the nerve agent tabun, as well as a physical barrier that dissolves in response to this analyte, we devise a network hydrogel that decomposes via a self-propagating cascade. A Meldrums acid-derived linker is incorporated into a hydrogel that undergoes a declick reaction in response to thiols, thereby breaking network connections, which releases more thiols, propagating the response throughout the gel. A combination of chemical reactions triggered by the addition of the tabun mimic initiates the cascade. The dissolving barrier is used to release dyes, as well as nanocrystals that undergo a spontaneous aggregation. Thus, this sensing system for tabun generates a physical response and the delivery of chemical agents in response to an initial trigger.

SUBMITTER: Lee DH

PROVIDER: S-EPMC8500376 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The goal was to test 14 nerve agent model compounds of soman, sarin, tabun, and cyclohexyl methylphosphonofluoridate (GF) for their suitability as substitutes for true nerve agents. We wanted to know whether the model compounds would form the identical covalent adduct with human butyrylcholinesterase that is produced by reaction with true nerve agents. Nerve agent model compounds containing thiocholine or thiomethyl in place of fluorine or cyanide were synthesized as Sp and Rp stereoisomers. Purified human butyrylcholinesterase was treated with a 45-fold molar excess of nerve agent analogue at pH 7.4 for 17 h at 21 degrees C. The protein was denatured by boiling and was digested with trypsin. Aged and nonaged active site peptide adducts were quantified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of the tryptic digest mixture. The active site peptides were isolated by HPLC and analyzed by MALDI-TOF-TOF mass spectrometry. Serine 198 of butyrylcholinesterase was covalently modified by all 14 compounds. Thiocholine was the leaving group in all compounds that had thiocholine in place of fluorine or cyanide. Thiomethyl was the leaving group in the GF thiomethyl compounds. However, sarin thiomethyl compounds released either thiomethyl or isopropyl, while soman thiomethyl compounds released either thiomethyl or pinacolyl. Thiocholine compounds reacted more rapidly with butyrylcholinesterase than thiomethyl compounds. Labeling with the model compounds resulted in aged adducts that had lost the O-alkyl group (O-ethyl for tabun, O-cyclohexyl for GF, isopropyl for sarin, and pinacolyl for soman) in addition to the thiocholine or thiomethyl group. The nerve agent model compounds containing thiocholine and the GF thiomethyl analogue were found to be suitable substitutes for true soman, sarin, tabun, and GF in terms of the adduct that they produced with human butyrylcholinesterase. However, the soman and sarin thiomethyl compounds yielded two types of adducts, one of which was thiomethyl phosphonate, a modification not found after treatment with authentic soman and sarin.

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A self-degradable hydrogel sensor for a nerve agent tabun surrogate through a self-propagating cascade.

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