Editing Disulfide (section)

===Reactions===
The most important aspect of disulfide bonds is their scission, as the {{chem2|S\sS}} bond is usually the weakest bond in an organic molecule.  Many specialized [[organic reaction]]s have been developed to cleave the bond. 

A variety of reductants reduce disulfides to [[thiols]].  Hydride agents are typical reagents, and a common laboratory demonstration "uncooks" eggs with [[sodium borohydride]].<ref>Hervé This. Can a cooked egg white be uncooked? The Chemical Intelligencer (Springer Verlag), 1996 (14), 51.  </ref>  Alkali metals effect the same reaction more aggressively: <chem display=block>RS-SR + 2 Na -> 2 NaSR,</chem> followed by protonation of the resulting metal thiolate: <chem display=block>NaSR + HCl -> HSR + NaCl</chem> 

In biochemistry labwork, thiols such as β-[[mercaptoethanol]] (β-ME) or [[dithiothreitol]] (DTT) serve as reductants through [[#Thiol-disulfide exchange|thiol-disulfide exchange]].  The thiol reagents are used in excess to drive the equilibrium to the right: <chem display=block>RS-SR + 2 HOCH2CH2SH <=> HOCH2CH2S-SCH2CH2OH + 2 RSH</chem>
The reductant [[TCEP|tris(2-carboxyethyl)phosphine]] (TCEP) is useful, beside being odorless compared to β-ME and DTT, because it is selective, working at both alkaline and acidic conditions (unlike DTT), is more hydrophilic and more resistant to oxidation in air. Furthermore, it is often not needed to remove TCEP before modification of protein thiols.<ref name=FT-242214>[http://www.interchim.fr/ft/2/242214.pdf TCEP technical information], from [[Interchim]]</ref>

In Zincke cleavage, halogens oxidize disulfides to a [[sulfenyl halide]]:<ref>{{multiref|
{{OrgSynth | first = Max H. | last = Hubacher | year = 1935 | title = ''o''-Nitrophenylsulfur Chloride| volume= 15|
doi= 10.15227/orgsyn.015.00452 | page = 45}}
|{{OrgSynth | first1 = Irwin B. | last1 = Douglass | first2 = Richard V. | last2 = Norton | year = 1960| title = Methanesulfinyl Chloride| volume = 40 | page = 62| doi=10.15227/orgsyn.040.0062}}
}}</ref><chem display=block>ArSSAr  +  Cl2  ->  2 ArSCl</chem>

More unusually, oxidation of disulfides gives first [[thiosulfinate]]s and then [[thiosulfonate]]s:<ref name=review>{{cite journal|title=Thiosulfonates: Synthesis, Reactions and Practical Applications|author=Nikolai S. Zefirov, Nikolai V. Zyk, Elena K. Beloglazkina, Andrei G. Kutateladze|journal=Sulfur Reports|year=1993|volume=14|pages=223–240|doi=10.1080/01961779308055018}}</ref>
:RSSR&nbsp;+ [O]&nbsp;→ RS(=O)SR
:RS(=O)SR&nbsp;+ [O]&nbsp;→ RS(=O)<sub>2</sub>SR

====Thiol-disulfide exchange====
In thiol–disulfide exchange, a [[thiol]]ate group {{chem2|\sS-}} displaces one [[sulfur]] [[atom]] in a disulfide bond {{chem2|\sS\sS\s}}. The original disulfide bond is broken, and its other sulfur atom is released as a new thiolate, carrying away the negative charge. Meanwhile, a new disulfide bond forms between the attacking thiolate and the original sulfur atom.<ref>{{cite book | last = Gilbert | first = H. F. | year = 1990 | chapter = Molecular and Cellular Aspects of Thiol–Disulfide Exchange | volume = 63 | pages = 69–172 | pmid = 2407068 | doi = 10.1002/9780470123096.ch2| title = Advances in Enzymology and Related Areas of Molecular Biology | isbn = 9780470123096 }}</ref><ref>{{cite book | last = Gilbert | first = H. F. | year = 1995 | doi = 10.1016/0076-6879(95)51107-5 | chapter = Thiol/disulfide exchange equilibria and disulfide bond stability | title = Biothiols, Part A: Monothiols and Dithiols, Protein Thiols, and Thiyl Radicals | series = [[Methods in Enzymology]] | volume = 251 | pages = 8–28 | pmid=7651233| isbn = 9780121821524 }}</ref>
[[File:Thiol disulfide exchange.png|center|frame|Thiol–disulfide exchange showing the linear intermediate in which the charge is shared among the three sulfur atoms. The thiolate group (shown in red) attacks a sulfur atom (shown in blue) of the disulfide bond, displacing the other sulfur atom (shown in green) and forming a new disulfide bond.]]
Thiolates, not thiols, attack disulfide bonds. Hence, thiol–disulfide exchange is inhibited at low [[pH]] (typically, below 8) where the protonated thiol form is favored relative to the deprotonated thiolate form. (The [[pKa|p''K''<sub>a</sub>]] of a typical thiol group is roughly 8.3, but can vary due to its environment.)

Thiol–disulfide exchange is the principal reaction by which disulfide bonds are formed and rearranged in a [[protein]]. The rearrangement of disulfide bonds within a protein generally occurs via intra-protein thiol–disulfide exchange reactions; a thiolate group of a [[cysteine]] residue attacks one of the protein's own disulfide bonds. This process of disulfide rearrangement (known as ''disulfide shuffling'') does not change the number of disulfide bonds within a protein, merely their location (i.e., which cysteines are bonded). Disulfide reshuffling is generally much faster than oxidation/reduction reactions, which change the number of disulfide bonds within a protein. The oxidation and reduction of protein disulfide bonds ''in vitro'' also generally occurs via thiol–disulfide exchange reactions. Typically, the thiolate of a redox reagent such as [[glutathione]], [[dithiothreitol]] attacks the disulfide bond on a protein forming a ''mixed disulfide bond'' between the protein and the reagent. 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.

The ''in vivo'' oxidation and reduction of protein disulfide bonds by thiol–disulfide exchange is facilitated by a protein called [[thioredoxin]]. This small protein, essential in all known organisms, contains two cysteine amino acid residues in a [[vicinal (chemistry)|vicinal]] arrangement (i.e., next to each other), which allows it to form an internal disulfide bond, or disulfide bonds with other proteins. As such, it can be used as a repository of reduced or oxidized disulfide bond moieties.