Coupling Activity‐Based Detection, Target Amplification, Colorimetric and Fluorometric Signal Amplification, for Quantitative Chemosensing of Fluoride Generated from Nerve Agents

Abstract

The G-class nerve agents, which include sarin, soman, and cyclosarin, react readily with nucleophilic reagents to produce fluoride. Thus, a chemosensing protocol has been designed for these agents that pairs the nucleophilic reactivity of oximates for generating fluoride with an autoinductive target amplification reaction to amplify the quantity of fluoride for facile colorimetric and fluorescent optical quantification. The chemosensing protocol was demonstrated by using the nerve agent surrogate diisopropyl fluorophosphate (DFP) and benzaldoxime as the nucleophile. Autoinductive fluoride amplification responds to fluoride released from DFP by amplifying the fluoride concentration and a yellow reporter molecule. The reporter is a conjugated oligomer with a nominal repeating unit that originates from 4-aminobenzaldehyde. Exposure of the amplified fluoride to a fluoride-specific ratiometric fluorescent reporter provides a fluorescent readout, in which three fluorophores are generated per fluoride. Both colorimetric and fluorescent readouts enable quantitative assays with low micromolar limits of detection for fluoride resulting from DFP. More importantly, this work demonstrates the successful merging of multiple complex reactions for achieving selective, sensitive, and quantitative chemosensing.

An Auto‐Inductive Cascade for the Optical Sensing of Thiols in Aqueous Media: Application in the Detection of a VX Nerve Agent Mimic

“…[6] Subsequently, aseries of auto-inductive cascades for signal amplification in response to fluoride or H 2 O 2 were developed by Shabat, [7] Phillips, [8] and others groups [9] including our own. [10] A unifying feature of these reactions is the involvement of quinomethide intermediates that result from the elimination of optical reporters and/or active reagents for auto-inductive cycling. [11] In previous studies,wehave used auto-inductive cascades to detect G-type phosphoryl-fluoride nerve-agent surrogates by monitoring fluoride generation upon reaction of the agents with oximates.…”

“…[11] In previous studies,wehave used auto-inductive cascades to detect G-type phosphoryl-fluoride nerve-agent surrogates by monitoring fluoride generation upon reaction of the agents with oximates. [10,12] In contrast, V-type nerve agents are thiophosphonate derivatives. [13] To the best of our knowledge, only Shabat has reported as elf-immolative probe for thiol self-propagation.…”

An Auto‐Inductive Cascade for the Optical Sensing of Thiols in Aqueous Media: Application in the Detection of a VX Nerve Agent Mimic

“…In 2009, an exponential amplification method was reported by Shabat for the detection of hydrogen peroxide based on a dendritic chain reaction (DCR) . Subsequently, a series of auto‐inductive cascades for signal amplification in response to fluoride or H 2 O 2 were developed by Shabat, Phillips, and others groups including our own . A unifying feature of these reactions is the involvement of quinomethide intermediates that result from the elimination of optical reporters and/or active reagents for auto‐inductive cycling …”

“…In previous studies, we have used auto‐inductive cascades to detect G‐type phosphoryl‐fluoride nerve‐agent surrogates by monitoring fluoride generation upon reaction of the agents with oximates . In contrast, V‐type nerve agents are thiophosphonate derivatives .…”

Self‐propagating amplification reactions for molecular detection and signal amplification: Advantages, pitfalls, and challenges

“…[9a, 9b, 9f, 15] The Anslyn group recently reported a six-fold release of fluoride for each fluoride trigger, amplifying both a colorimetric and fluorescence response (compound 10 ). [23] Phillips also designed self-powered polymeric materials (compounds 12 and 13 , Figure 2) by incorporating a fluoride self-propagating auto-inductive reaction directly onto polymers. [9c, 9d] TentaGel microsphere 12 converted UV light signals into initiating the pumping of the surrounding fluid, and responded autonomously and continuously after removing the fleeting stimuli.…”