LAUSR

Gasotransmitters and related reactive sulfur, oxygen, and nitrogen species such as nitric oxide (NO), hydrogen sul-fide (H2S), carbon monoxide (CO), hydrogen peroxide (H2O2) and downstream products like peroxynitrite (ONOO-), polysulfides (HSnH), hydroxyl radical (HO•), and azanone (nitroxyl, HNO) are produced under physiological condi-tions and impact cellular signaling and stress. Evolution-ary pressures have driven life to develop sophisticated mechanisms to control the formation and response to this complex reactive species interactome, making it a critical fulcrum that balances health and disease in human physiol-ogy. Driven by a need to understand and measure these types of reactive species, the last decade has witnessed ex-tensive research activity in developing reaction-based probes for optical detection and imaging of reactive sulfur, oxygen, and nitrogen species in living systems. - The cen-tral advantage of this approach is that it is compatible with living cells and animals, thereby enabling the direct detec-tion of transient reactive species as they are produced in the intact specimen. This gives the potential for optical imag-ing with high spatial and temporal resolution. The general approach for a reaction-based probe (also referred to as an activity-based probe) is to design and implement chemose-lective and biocompatible reactions, whereby a functional group on the probe molecule reacts with an analyte of inter-est with selectivity versus other biological molecules. A large number of functional group triggers have been devel-oped to detect various analytes. The detection chemistry must act to switch the molecular properties in such a way that the reaction with an analyte is translated into an ob-servable optical output. This translation can be the direct result of the reaction or mediated by spontaneous self-immolative cascades. Modulating the optical properties has been accomplished by using triggering chemistry for in situ fluorophore synthesis from a non-luminescent precur-sor, attenuation of photoinduced electron transfer (PET) quenching, or altering the emission properties by modulat-ing the internal charge transfer properties of a fluoro-phore.4,7 While fluorescence has been the most widely ex-plored optical response, phosphorescence and long-lived luminescence, bioluminescence, chemiluminescence, photoacoustic, and other modalities are being explored.