Disulfide

In chemistry, a disulfide (or disulphide in British English) is a compound containing a R−S−S−R′ functional group or the S2−2 anion.

In inorganic chemistry, the anion appears in a few rare minerals, but the functional group has tremendous importance in biochemistry.

Disulfide bridges formed between thiol groups in two cysteine residues are an important component of the tertiary and quaternary structure of proteins.

The S-S bond length is 2.03 Å in diphenyl disulfide,[1] similar to that in elemental sulfur.

Furthermore, reflecting the polarizability of divalent sulfur, the S−S bond is susceptible to scission by polar reagents, both electrophiles and especially nucleophiles (Nu):[3]

[5] The transformation is depicted as follows: A variety of oxidants participate in this reaction including oxygen and hydrogen peroxide.

In the laboratory, iodine in the presence of base is commonly employed to oxidize thiols to disulfides.

Several metals, such as copper(II) and iron(III) complexes affect this reaction.

In the converse reaction, carbanionic reagents react with elemental sulfur to afford mixtures of the thioether, disulfide, and higher polysulfides.

Reagents that deliver the equivalent of "RS+" react with thiols to give asymmetrical disulfides:[5] where R″2N is the phthalimido group.

Hydride agents are typical reagents, and a common laboratory demonstration "uncooks" eggs with sodium borohydride.

In biochemistry labwork, thiols such as β-mercaptoethanol (β-ME) or dithiothreitol (DTT) serve as reductants through thiol-disulfide exchange.

The original disulfide bond is broken, and its other sulfur atom is released as a new thiolate, carrying away the negative charge.

The oxidation and reduction of protein disulfide bonds in vitro also generally occurs via thiol–disulfide exchange reactions.

This mixed disulfide bond when attacked by another thiolate from the reagent, leaves the cysteine oxidized.

In effect, the disulfide bond is transferred from the protein to the reagent in two steps, both thiol–disulfide exchange reactions.

[4] Since most cellular compartments are reducing environments, in general, disulfide bonds are unstable in the cytosol, with some exceptions as noted below, unless a sulfhydryl oxidase is present.

[14] Disulfide bonds in proteins are formed between the thiol groups of cysteine residues by the process of oxidative folding.

Disulfide bonds play an important protective role for bacteria as a reversible switch that turns a protein on or off when bacterial cells are exposed to oxidation reactions.

Hydrogen peroxide (H2O2) in particular could severely damage DNA and kill the bacterium at low concentrations if not for the protective action of the SS-bond.

[16] In eukaryotic cells, in general, stable disulfide bonds are formed in the lumen of the RER (rough endoplasmic reticulum) and the mitochondrial intermembrane space but not in the cytosol.

The virus Vaccinia also produces cytosolic proteins and peptides that have many disulfide bonds; although the reason for this is unknown presumably they have protective effects against intracellular proteolysis machinery.

In chloroplasts, for example, the enzymatic reduction of disulfide bonds has been linked to the control of numerous metabolic pathways as well as gene expression.

In this way chloroplasts adjust the activity of key processes such as the Calvin–Benson cycle, starch degradation, ATP production and gene expression according to light intensity.

Additionally, It has been reported that disulfides plays a significant role on redox state regulation of Two-component systems (TCSs), which could be found in certain bacteria including photogenic strain.

[18] Over 90% of the dry weight of hair comprises proteins called keratins, which have a high disulfide content, from the amino acid cysteine.

The robustness conferred in part by disulfide linkages is illustrated by the recovery of virtually intact hair from ancient Egyptian tombs.

The high sulfur content of hair and feathers contributes to the disagreeable odor that results when they are burned.

Examples: Aside from the major role in biology, disulfides are found in rubber that has been vulcanized with sulfur.

[20] Although the exact mechanism underlying the vulcanization process is not entirely understood (as multiple reaction pathways are present but the predominant one is unknown), it has been extensively shown that the extent to which the process is allowed to proceed determines the physical properties of the resulting rubber—namely, a greater degree of crosslinking corresponds to a stronger and more rigid material.