Imidazolyl disulfide

The 2-pyridyl and related 2-imidazolyl disulfides have found special use in the closure of large lactone rings.118 This type of structure is encountered in a number of antibiotics which, because of the presence of numerous other sensitive functional groups, require mild conditions for cyclization. It has been suggested that the pyridyl and imidazoyl thioesters function by a mechanism in which the heterocyclic nitrogen acts as... 

In acetic acid solution 30% hydrogen peroxide converts 2-imidazolyl methyl sulfides into sulfones" " and sometimes sulfoxides. In tri-fluoracetic acid the sulfoxides are formed preferentially periodate, too, can give the sulfoxides. Oxidation of 4-mercaptoimidazoles under mild conditions gives bis(4-imidazolyl) disulfides which can be cleaved by hydrogen sulfide. With 15% alkaline hydrogen peroxide at 90°C the sulfonic acid is the major product. Imidazole-5-sulfonyl chlorides give sulfonamides... 

Jordan BF, Runquist M, Raghunand N et al. The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging. Clin Cancer Res 2005 11 529-536. 

A continuing search for superior reagents for this cyclization has revealed that various bis-2-imidazolyl disulfides offer significant improvements in both yields and rates of reaction. The disulfide (1) is particularly promising. ... 

In summary, protein molecules may contain up to nine amino acids that are readily derivatizable at their side chains aspartic acid, glutamic acid, lysine, arginine, cysteine, histidine, tyrosine, methionine, and tryptophan. These nine residues contain eight principal functional groups with sufficient reactivity for modification reactions primary amines, carboxylates, sulfhydryls (or disulfides), thioethers, imidazolyls, gua-nidinyl groups, and phenolic and indolyl rings. All of these side chain functional groups in addition to the N-terminal a-amino and the C-terminal a-carboxylate form the full complement of polypeptide reactivity within proteins (Fig. 12). 

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