Bimanes 28: Extraction of sulfur from fluorescent models for biological thiols

Sulfur extraction from the tripeptide thiol, glutathione (α-glu-cys-gly) ( 1 ) via reaction with syn-(1-bromo-ethyl, methyl)bimane ( 2 ) yields glutathione slfide and the thiabridged bimane, μ(S)-syn-(methylmethylene, methyl)bimane ( 3 ) 1]. The reaction with 2 has been extended to dithiols as models for important biological thiols such as reduced trypanothione. The fluorescent dithiols were derived through reductive cleavage with triphenylphosphine (tetrahydrofuan, Hcl?Kbr solution, pH 1.5) of the dithiatriclic bimane esters, μ(O₂C(CH₂)SS(CH₂)_nCO₂)-syn-(CH₂,CH₃)B, n = 1, 2, 3, prepared from syn-(bromomethyl, methyl)bimane ( 4 ) and the corresponding dithiadicarboxylic acids. Sulfur extraction led to 3 and the cyclic sulfide derived from the dithiol in moderate yields. The dithiols, dithiothreitol and dithioerythritol, also yielded moderate amounts of 3 . Sterically hindered thiols (e.g., those in hemoglobin) gave 3 in lower yields. Treatment of human red blood cells and red cells membranes (hemoglobin-free ghosts) with 2 gave rise to some 3 . A side product in some reactions was the oxabridged bimane, μ(O)-syn-(methylmethylene, methyl)bimane.