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Updated: Jun 13, 2026

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals
Published on: April 19, 2019
1,9-Bis(2-pyridyl)-1,2,8,9-tetrathia-5-oxanonane
1Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA.
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Disulfide crosslinking of proteins is typically performed by treating proteins bearing cysteine residues with small-molecule disulfide reagents. The process results in the formation of a mixed disulfide intermediate, which then reacts with the cysteine residue of another protein molecule to form the crosslinked product. This second step requires the intimate association of two large reactants. The ensuing steric hindrance can result in poor crosslinking yields. Here, we introduce a bis(disulfide) reagent in which activated disulfides are separated by linkers that can alleviate steric hindrance and thereby potentially increase the efficiency of crosslinking.
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