ABSTRACT
An unprecedented intramolecular [4 + 2] tetrazine-olefin cycloaddition with α,ß-unsaturated substrates was discovered. The reaction produces unique coumarin-dihydropyridazine heterocycles that exhibited strong fluorescence with large Stokes shifts and excellent photo- and pH-stability. This property can be used for reaction analysis. The rate of cycloaddition was found to be solvent dependent and was determined using experimental data with a kinetic modeling software (COPASI) as well as DFT calculations (k 1 = 0.64 ± 0.019 s-1 and 4.1 s-1, respectively). The effects of steric and electronic properties of both the tetrazine and α,ß-unsaturated carbonyl on the reaction were studied and followed the known trends characteristic of the intermolecular reaction. Based on these results, we developed a "release-then-click" strategy for the ROS triggered release of methylselenenic acid (MeSeOH) and a fluorescent tracer. This strategy was demonstrated in HeLa cells via fluorescence imaging.
ABSTRACT
Sulfane sulfur species such as hydropersulfides (RSSH), polysulfides (RSnR), and hydrogen polysulfides (H2Sn) are critically involved in sulfur-mediated redox signaling, but their detailed mechanisms of action need further clarification. Therefore, there is a need to develop selective and sensitive sulfane sulfur detection methods to gauge a better understanding of their functions. This review summarizes current detection methods that include cyanolysis, chemical derivatization and mass spectrometry, proteomic analysis, fluorescent probes, and resonance synchronous/Raman spectroscopic methods. The design principles, advantages, applications, and limitations of each method are discussed, along with suggested directions for future research on these methods. The development of robust detection methods for sulfane sulfur species will help to elucidate their mechanisms and functions in biological systems.
