Synthesis and Redox Properties of Water-Soluble Asymmetric Trityl Radicals

Tetrathiatriarylmethyl (trityl) radicals have been recently shown to react with biological oxidoreductants including glutathione (GSH), ascorbic acid (Asc), and superoxide anion radical (O-2(center dot-)). However, how the substituents affect the reactivity of trityl radicals is still unknown. In this work, five asymmetric trityl radicals were synthesized and their reactivities with GSH, Asc, and O-2(center dot-)-investigated. Under aerobic conditions, GSH induces fast decays for the thioether-(TSA) and Nmethyleneglycine-substituted (TGA) derivatives and slow decay for the 4-carboxyphenyl-containing one (TPA). Under anaerobic conditions, the direct reduction of these radicals by GSH also occurs with rate constants (k(GSH)) from 1.8 x 10(-4) M-1 s(-1) for TPA to 1.0 x 10(-2) M-1 s(-1) for TGA. Moreover, these radicals can also react with O-2(center dot-) with rate constants (k(SO)) from 1.2 x 10(3) M-1 s(-1) for ET-01 to 1.6 x 10(4) M-1 s(-1) for TGA. Surprisingly, these radicals are completely inert to Asc in both aerobic and anaerobic conditions. Additionally, the substituents exert an important effect on redox potentials of these trityl radicals. This work demonstrates that the redox properties of the trityl radicals strongly depend on their substituents, and TPA with high stability toward GSH shows great potential for intracellular applications.