Sensors provide powerful tools and technologies to peer into the natural world, enabling researchers to discover and decipher new molecular phenomena through the design, construction, and application of chemical probes. Indeed, the invention of new sensors drives the ability to literally create new types of experiments across a variety of different length and time scales, bringing together chemists from core areas of organic, inorganic, physical, biological, and analytical chemistry together with biologists, physicists, and engineers in synergistic ways. At its core, fundamental and applied research in chemical sensors requires molecular-level selectivity in complex environments, and in this context, the search for selectivity has primarily focused on binding-based approaches derived from molecular recognition, akin to the lock-and-key constructs that endow enzymes and other biological systems with exquisite specificity. Along these lines, the origins of supramolecular host–guest chemistry have launched an entire field of molecular sensors and molecular logic gates, and traditional sensors use principles from this biomimetic and bioinspired chemistry.
An alternative, emerging strategy to sensor design is through the use of dynamic molecular reactivity, rather than static molecular recognition and binding, to achieve such specificity giving rise to a growing field of “Activity-Based Sensing.” This approach is particularly attractive for situations in which the analyte of interest is of similar size and shape to others in a complex biological or environmental milieu and/or is transiently produced and metabolized in a given spatial and temporal context. In this special issue of Accounts of Chemical Research, selected leading research groups across the international stage address fundamental questions and frontier applications in activity-based sensing, as well as share their latest results and forward-looking prospects in an exciting new field of science and engineering. A broad range of topics in the sensor field, spanning principles of selectivity and signal enhancement as well as probes for particular chemical species, to various types of imaging modalities and classes of molecular and materials sensing scaffolds, to their application in proteomics and the design of innovative diagnostics and therapeutics, is covered in this special issue.
The scientific breadth of the articles collected in this special issue highlights the wealth of new opportunities in the field. Several articles focus on new reaction development and sensor/receptor displacement strategies to target specific analytes of biological importance, spanning reactive oxygen, reactive nitrogen, and reactive sulfur species to epigenetic enzymes and nucleic acids to metal cations and related anions to redox and voltage signaling and membrane potentials to emerging one-carbon signals such as carbon monoxide and formaldehyde. Other articles contribute to activity-based sensing in the context of emerging imaging modalities, including functional magnetic resonance imaging, photoacoustic imaging, and chemiluminescence imaging. New molecules and materials that undergo cascade processes and aggregation induced emission (AIE) show a continuum between soluble molecular probes and more complex molecular aggregates. Fundamental physical mechanisms such as photoinduced electron transfer, internal charge transfer, Forster/Dexter energy transfer, restriction of intramolecular motion, and chemiluminescence/bioluminescence form the foundation for many sensor designs. Finally, although many of the articles focus on imaging applications of activity-based sensing, proteomics and drug discovery, diagnostics, as well as combined theranostic applications from targeted, functional release of cargo offer other new avenues to pursue.
We hope that readers will enjoy the quality and diversity of the topics collected in this special issue and be encouraged to expand the frontiers of the field together.