| Autor: |
Hu Q; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, North Carolina 27101, United States., Zhu C; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, North Carolina 27101, United States., Hankins RA; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, North Carolina 27101, United States., Murmello AR; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, North Carolina 27101, United States., Marrs GS; Department of Biology, Wake Forest University, Winston-Salem, North Carolina 27109, United States., Lukesh JC 3rd; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, North Carolina 27101, United States. |
| Abstrakt: |
Hydrogen sulfide (H 2 S), an endogenous signaling molecule, is known to play a pivotal role in neuroprotection, vasodilation, and hormonal regulation. To further explore the biological effects of H 2 S, refined donors that facilitate its biological delivery, especially under specific (patho) physiological conditions, are needed. In the present study, we demonstrate that ortho -substituted, aryl boronate esters provide two unique and distinct pathways for H 2 S release from thioamide-based donors: Lewis acid-facilitated hydrolysis and reactive oxygen species (ROS)-induced oxidation/cyclization. Through a detailed structure-activity relationship study, donors that resist hydrolysis and release H 2 S solely via the latter mechanism were identified, which have the added benefit of providing a potentially useful heterocycle as the lone byproduct of this novel chemistry. To highlight this, we developed an ROS-activated donor ( QH642 ) that simultaneously synthesizes a benzoxazole-based fluorophore en route to its H 2 S delivery. A distinct advantage of this design over earlier self-reporting donors is that fluorophore formation is possible only if H 2 S has been discharged from the donor. This key feature eliminates the potential for false positives and provides a more accurate depiction of reaction progress and donor delivery of H 2 S, including in complex cellular environments. |
