Stimuli-Responsive Polymer Film that Autonomously Translates a Molecular Detection Event into a Macroscopic Change in Its Optical Properties via a Continuous, Thiol-Mediated Self-Propagating Reaction

Abstract

This Communication describes a chemically responsive polymer film that is capable of detecting low levels of a specific applied molecular signal (thiol) and subsequently initiating a self-propagating reaction within the material that converts the nonfluorescent film into a globally fluorescent material. We illustrate that the intensity of the resulting fluorescent material is independent of the quantity of the applied thiol, whereas the rate to reach the maximum level of signal is directly proportional to the quantity of the signal. In contrast, a control film, which lacks functionality for mediating the self-propagating reaction, provides a maximum change in fluorescence that is directly proportional to the quantity of the applied thiol. This level of nonamplified signal is 78% lower in intensity (when initiated with 100 μM of applied thiol) than is achieved when the material contains functionality that supports the self-powered, self-propagating amplification reaction.

Figure 1

Illustration of a polymeric film that transforms completely from nonfluorescent to fluorescent when exposed to trace levels of added thiol. The added thiol initiates a self-propagating reaction within the film that amplifies the fluorescent output. The bottom half of the figure depicts the specific polymer (1) and self-propagating reaction that provides the global change from nonfluorescent to fluorescent across the entire material.

Figure 2

Demonstration that monomer 8 is capable of supporting the self-propagating reaction. (a) The reaction conditions and products when 8 is exposed to thiol (cysteine in this example). (b) LCMS chromatograms that reveal the temporal change in concentration of reactants and products when 8 (2 mM) in 1:1 MeCN–buffered water (pH 7.4) is exposed to 0.1 equiv of l-cysteine at 23 °C. (c) Kinetics (obtained from fluorescence measurements) that support the self-propagating reaction in (a). These results demonstrate that even trace levels of added thiol elicit a maximum fluorescence response over time. The graph includes all data corresponding to three replicates per equivalent of added cysteine. The inset clarifies the response for 1 equiv of cysteine. The λ_ex for coumarin 11 is 320 nm, while the λ_em is 380 nm. The lines are simulated data for the reaction A + B → C + A (see the text for details) superimposed on the experimental data points.

Figure 3

Self-propagating reactions in films. (a,b) Change in IR signature in the carbonyl region when a film of 1 (a) or 10 (b) is exposed to 10 mM thiol (l-cysteine) in 1:1 MeCN–buffered water (pH 7.4) for 3 h. (c) Kinetics (obtained from fluorescence measurements) when 0.1 mM (pink data), 1 mM (blue data), and 10 mM (black data) solutions of l-cysteine were exposed to films of polymers 1 and 10 at 23 °C. The circular data points correspond to films made from 1; the triangular data in the inset graph correspond to films made from 10 (the axis labels are the same as the larger graph). The data represent the averages of three measurements, and the error bars reveal the standard deviations from these averages. In the context of solid state films, the λ_ex = 320 nm; λ_em = 430 nm. The lines are provided to visually differentiate the data sets.

Scheme 1. Synthesis of Polymer 1 and Control Polymer 10a

^aReagents and conditions: (a) BrCH₂CO₂tBu, NaHCO₃, 70 °C, DMF (42%); (b) TFA, CH₂Cl₂; (c) HBTU, DIEA, DMAP, MeCN (42% over 2 steps); (d) DNBS-Cl, DIEA, CH₂Cl₂, −78 to 20 °C (87%); (e) K₂CO₃, 18-crown-6, THF, −20 °C (66% for 8 and 43% for 9); (f) (i) Grubb’s second gen. cat., CH₂Cl₂, 20 °C; (ii) ethyl vinyl ether (81% for 1 and 82% for 10).