Related Experiment Video
Updated: Oct 26, 2025

Synthesis of a Thiol Building Block for the Crystallization of a Semiconducting Gyroidal Metal-sulfur Framework
Published on: April 9, 2018
Single-step Replacement of an Unreactive C-H Bond by a C-S Bond Using Polysulfide as the Direct Sulfur Source in
Ronghai Cheng1, Lian Wu2,3,4, Rui Lai1
1Department of Chemistry, Boston University, Boston, MA 02215, USA.
Abstract:
Ergothioneine, a natural longevity vitamin and antioxidant, is a thiol-histidine derivative. Recently, two types of biosynthetic pathways were reported. In the aerobic ergothioneine biosynthesis, a non-heme iron enzyme incorporates a sulfoxide to an sp2 C-H bond in trimethyl-histidine (hercynine) through oxidation reactions. In contrast, in the anaerobic ergothioneine biosynthetic pathway in a green sulfur bacterium, Chlorobium limicola, a rhodanese domain containing protein (EanB) directly replaces this unreactive hercynine C-H bond with a C-S bond. Herein, we demonstrate that polysulfide (HSSnSR) is the direct sulfur-source in EanB-catalysis. After identifying EanB's substrates, X-ray crystallography of several intermediate states along with mass spectrometry results provide additional mechanistic details for this reaction. Further, quantum mechanics/molecular mechanics (QM/MM) calculations reveal that protonation of Nπ of hercynine by Tyr353 with the assistance of Thr414 is a key activation step for the hercynine sp2 C-H bond in this trans-sulfuration reaction.
Related Concept Videos
Preparation and Reactions of Sulfides
Sulfur Assimilation
Preparation and Reactions of Thiols
Electrophilic Aromatic Substitution: Sulfonation of Benzene
Structure and Nomenclature of Thiols and Sulfides
Radical Substitution: Hydrogenolysis of Alkyl Halides with Tributyltin Hydride
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation...

