Biodegradable Paper Sensor Functionalized with Oxidized Bisindolylmethane for Temporal Discrimination of Hazardous Organophosphorus Simulants in Aqueous Media

Abstract

Organophosphorus (OP) nerve agents pose significant threats to human health, chemical warfare scenarios, and biomarker-based exposure assessment, necessitating rapid, selective, and field-deployable detection strategies. Here, we report the design and synthesis of oxidized bisindolylmethane (BIM) derivatives capable of discriminating OP simulants in pure aqueous buffered media. Comparative studies of hydroxyl and methoxy-substituted derivatives revealed distinct sensing mechanisms governed by electronic and hydrogen-bonding effects. The hydroxyl-functionalized probe (probe 1) undergoes an initial phosphorylation step common to both diethyl cyanophosphate (DCNP) and diethyl chlorophosphate (DCP), producing an immediate colorimetric shift from orange to yellow. Critically, a subsequent time-dependent Michael addition occurs exclusively with DCNP, converting the yellow solution to colorless and enabling temporal differentiation between structurally similar OP analogues, with a limit of detection of 6.8 ± 0.3 μM (for DCNP). In contrast, the methoxy-substituted probe (probe 2) initially engages in hydrogen-bonding interactions with both DCP and DCNP; however, Michael addition proceeds only with DCNP, generating a faster, time-dependent decrease in absorbance. Furthermore, integration of these probes onto biodegradable cellulose paper strips provides a low-cost, portable, and aqueous-compatible platform for rapid, visual detection, where distinct color transitions reflect both immediate and time-dependent chemical transformations. Overall, this study presents a sustainable, environmentally compatible sensing platform that combines mechanistic insight, high selectivity, and practical deployability for real-time monitoring of OP nerve agent mimics and other hazardous analytes.