Mass spectrometric monitoring of redox transformation and arylation of tryptophan

Abstract

Tryptophan (Trp) is an essential amino acid obtained from human diet. It is involved not only in de novo biosynthesis of proteins but also in complex metabolic pathways. Redox transformation of tryptophan is under-explored in comparison with kynurenine, serotonin and indole pyruvate pathways. We described herein a mass spectrometric approach that can not only detect electron transfer-associated changes in masses and charges, but also identify electron-directed bond cleavages and radical-radical cross-coupling reactions in redox transformation of tryptophan. Photoactive TiO₂ that is widely applied in cosmetic products is used as electron donor and receptor because of the capability to generate photoelectrons and holes. It was demonstrated tryptophan undergoes redox transformation through the removal of an electron from amino nitrogen atom by hole oxidization along with an electron capture in the indole ring. The back and forth electron-shuttle converts electric energy into chemical energy that enforces bond cleavages. Sodium-coupled electron transfer (SCET) was found in complementary with proton-coupled electron transfer in tryptophan. The movement of sodium ions avoids electric charge buildup caused by electron transfer. Various redox products were detected on both light irradiated TiO₂ and skins, among which β-carboline shows extensive radical scavenging ability for diverse cross-coupling with indole derivatives. Light-independent redox products have been detected in vivo such as in mouse brain, indicating the presence of in vivo electron transfer-directed redox transformation. It has also been revealed that tryptophan can be arylated on C_α and C_β atoms in response to the exposure of halogenated aromatics.