Hydrogen sulfide (H2S) is an important biological signaling molecule that has been recognized alongside nitric oxide and carbon monoxide as being a small gasotransmitter that is enzymatically produced and impacts multiple physiological functions. To detect hydrogen sulfide, there has been a focus on developing fluorescent probes to target particular analytes; however, fluorescent probes lack sensitivity and depth penetration due to background autofluorescence and light scattering. Chemiluminescence does not require light excitation, which greatly reduces the amount of autofluorescence and photoactivation.
In order to detect hydrogen sulfide in living systems with high sensitivity, a series of sterically stabilized 1,2-dioxetane chemiluminescent reduction-reaction based hydrogen sulfide probes have been synthesized. These probes are prepared in 10-11 synthetic steps, with key transformations including a Horner-Wadsworth-Emmons reaction to form a tetra- substituted enol ether, a Mitsunobu reaction to install the sensing trigger, and a versatile Heck reaction to append electron-withdrawing groups. The final preparation of the sterically crowded 1,2-dioxetane proceeds in high yields and is accomplished by a [2+2] cycloaddition with singlet oxygen generated by an energy pooling mechanism from triplet oxygen and the triplet state of methylene blue accessed via visible light irradiation. The appendage of an acetoxymethyl ester enables cell-trappability and enhances utility for monitoring hydrogen sulfide in living cells. These newly synthesized hydrogen sulfide chemiluminescent probes have been tested at a physiological relevant pH both in vitro and in living systems.
This dissertation contains the synthesis and characterization of two new hydrogen sulfide chemiluminescent probes, CHS-4 and CHS-5-AM.
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Bezner, Briley, "Cell-Trappable Chemiluminescent Probes For Monitoring Hydrogen Sulfide in Living Cells" (2019). Chemistry Theses and Dissertations. 14.