Poly(carboxypyrrole)s That Depolymerize from Head to Tail in the Solid State in Response to Specific Applied Signals.

This Article describes the design, synthesis, and analysis of a new class of polymer that is capable of depolymerizing continuously, completely, and cleanly from head to tail when a detection unit on the head of the polymer is exposed to a specific applied signal. The backbone of this polymer consists of 1,3-disubstituted pyrroles and carboxy linkages similar to polyurethanes. Diverse side chains or reactive end-groups can be introduced readily, which provides modular design of polymer structure. The designed depolymerization mechanism proceeds through spontaneous release of carbon dioxide and azafulvene in response to a single triggering reaction with the detection unit. These poly(carboxypyrrole)s depolymerize readily in nonpolar environments, and even in the bulk as solid-state plastics.

A Strategy for Minimizing Background Signal in Autoinductive Signal Amplification Reactions for Point-of-Need Assays.

Rapid point-of-need assays are used to detect abundant biomarkers. The development of in situ signal amplification reactions could extend these assays to screening and triaging of patients for trace levels of biomarkers, even in resource-limited settings. We, and others, have developed small molecule-based in situ signal amplification reactions that eventually may be useful in this context. Herein we describe a design strategy for minimizing background signal that may occur in the absence of the target analyte, thus moving this in situ signal amplification approach one step closer to practical applications. Specifically, we describe allylic ethers as privileged connectors for linking detection and propagating functionality in a small molecule signal amplification reagent. Allylic ethers minimize background reactions while still enabling controlled release of a propagating signal in order to continue the signal amplification reaction. This paper characterizes the ability of allylic ethers to provide an amplified response, and offers insight into additional design considerations that are needed before in situ small molecule-based signal amplification becomes a viable strategy for point-of-need diagnostics.

Design, Synthesis, and Characterization of Small-Molecule Reagents That Cooperatively Provide Dual Readouts for Triaging and, When Necessary, Quantifying Point-of-Need Enzyme Assays.

A newly designed small molecule reagent provides both qualitative and quantitative readouts in assays that detect enzyme biomarkers. The qualitative readout enables rapid triaging of samples so that only samples that contain relevant concentrations of the target analyte must be quantified. The reagent is accessible in essentially three steps and 34% overall yield, is stable as a solid when heated to 44 °C for >1 month, and does not produce background signal when used in an assay. This paper describes the design and synthesis of the reagent, characterizes its response properties, and establishes the scope of its reactivity.