An Expanded Palette of Fluorescent COS/H₂S‐Releasing Donors for H₂S Delivery, Detection, and In Vivo Application

Hydrogen sulfide (H 2 S) is an important reactive sulfur species that is involved in many biological functions, and H 2 S imbalances have been indicated as a potential biomarker for various diseases. Different H 2 S donors have been developed to deliver H 2 S directly to biological systems, but few reports include donors with optical responses that allow for tracking of H 2 S release. Moreover, donor systems that use the same chemistry to deliver H 2 S across a palette of fluorescent responses remain lacking. Here we report five thiol‐activated fluorescence turn‐on COS/H 2 S donors that utilize blue, yellow, orange, red, and near infrared‐emitting dyes functionalized with an H 2 S‐releasing sulfenyl thiocarbonate scaffold. Upon treatment with thiols, each donor provides a fluorescence turn‐on response (3–310‐fold) and high H 2 S release efficiencies (>60 %). Using combined electrode and fluorescence experiments, we directly correlate the measured H 2 S release with the fluorescence response. All donors are biocompatible and release H 2 S in live cell environments. In addition, we demonstrate that the NIR donor allows for imaging H 2 S release in live rats via subcutaneous injection of the donor loaded into an alginate gel, which to the best of our knowledge is the first in vivo tracking of H 2 S release from a fluorogenic donor in non‐transparent organisms.