An Expanded Palette of Fluorescent COS/HS-Releasing Donors for HS Delivery, Detection, and In Vivo Application.

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