Inchemistry, adisulfide (ordisulphide inBritish English) is a compound containing aR−S−S−R′functional group or theS2−
2anion. Ininorganic chemistry, the anion appears in a few rare minerals. Compounds of the formR−S−S−H are usually calledpersulfides instead.
Disulfide bridges also appear as a commonpost-translational modification in proteins.
Disulfides have a C–S–S–Cdihedral angle approaching 90°. The S–S bond length is 2.03 Å indiphenyl disulfide,[1] similar to that in elemental sulfur.
Disulfides are usually symmetric but they can also be unsymmetric. Symmetrical disulfides are compounds of the formulaRSSR. Most disulfides encountered in organosulfur chemistry are symmetrical disulfides.Unsymmetrical disulfides (also calledheterodisulfides ormixed disulfides) are compounds of the formulaRSSR'. Unsymmetrical disulfide are less common in organic chemistry, but many disulfides in nature are unsymmetrical.
Disulfides can be components of rings.Lipoic acid, a1,2-dithiolane is a major example. Rings with more than one disulfide usually tend to polymerize.[2]
Thiuram disulfides, with the formula (R2NCSS)2, are disulfides but they behave distinctly because of thethiocarbonyl group.
Disulfide bonds are strong, with a typicalbond dissociation energy of 60 kcal/mol (251 kJ mol−1). However, being about 40% weaker thanC−C andC−H bonds, the disulfide bond is often the "weak link" in many molecules. Furthermore, reflecting thepolarizability of divalent sulfur, theS−S bond is susceptible to scission by polar reagents, bothelectrophiles and especiallynucleophiles (Nu):[3]
The disulfide bond is about 2.05 Å in length, about 0.5 Å longer than aC−C bond. Rotation about theS−S axis is subject to a low barrier. Disulfides show a distinct preference fordihedral angles approaching 90°. When the angle approaches 0° or 180°, then the disulfide is a significantly better oxidant.
Disulfides where the two R groups are the same are called symmetric, examples beingdiphenyl disulfide anddimethyl disulfide. When the two R groups are not identical, the compound is said to be an asymmetric or mixed disulfide.[4]
Although thehydrogenation of disulfides is usually not practical, the equilibrium constant for the reaction provides a measure of the standard redox potential for disulfides:
This value is about −250 mV versus thestandard hydrogen electrode (pH = 7). By comparison, the standard reduction potential forferrodoxins is about −430 mV.
Disulfide bonds are usually formed from theoxidation ofthiol (−SH) groups, especially in biological contexts.[5] The transformation is depicted as follows:
A variety of oxidants participate in this reaction including oxygen andhydrogen peroxide. Such reactions are thought to proceed viasulfenic acid intermediates. 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.[6] Alternatively, disulfide bonds in proteins often formed bythiol-disulfide exchange:
Such reactions are mediated by enzymes in some cases and in other cases are under equilibrium control, especially in the presence of a catalytic amount of base.
Thealkylation of alkali metal di- andpolysulfides gives disulfides. "Thiokol" polymers arise whensodium polysulfide is treated with an alkyl dihalide. In the converse reaction, carbanionic reagents react with elemental sulfur to afford mixtures of the thioether, disulfide, and higher polysulfides. These reactions are often unselective but can be optimized for specific applications.
Many specialized methods have been developed for forming unsymmetrical disulfides. Reagents that deliver the equivalent of "RS+" react with thiols to give asymmetrical disulfides:[5]
whereR″2N is thephthalimido group.Bunte salts, derivatives of the typeRSSO−3Na+are also used to generate unsymmetrical disulfides:[7]
The most important aspect of disulfide bonds is their scission, as theS−S bond is usually the weakest bond in an organic molecule.[citation needed] Many specializedorganic reactions have been developed to cleave the bond.
A variety of reductants reduce disulfides tothiols. Hydride agents are typical reagents, and a common laboratory demonstration "uncooks" eggs withsodium borohydride.[8] Alkali metals effect the same reaction more aggressively: followed by protonation of the resulting metal thiolate:In biochemistry labwork, thiols such as β-mercaptoethanol (β-ME) ordithiothreitol (DTT) serve as reductants throughthiol-disulfide exchange. The thiol reagents are used in excess to drive the equilibrium to the right:The reductanttris(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.[9]
In Zincke cleavage, halogens oxidize disulfides to asulfenyl halide:[10]More unusually, oxidation of disulfides gives firstthiosulfinates and thenthiosulfonates:[11]
In thiol–disulfide exchange, athiolate group−S− displaces onesulfuratom in a disulfide bond−S−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.[12][13]
Thiolates, not thiols, attack disulfide bonds. Hence, thiol–disulfide exchange is inhibited at lowpH (typically, below 8) where the protonated thiol form is favored relative to the deprotonated thiolate form. (ThepKa of a typical thiol group is roughly 8.3, but can vary due to its environment.) Thiol-disulfide exchange is an important process for the formation of the correctdisulfide bridges in proteins and to keep cysteine from unwanted oxidation during lab experiments.
Thiosulfoxides are isomeric with disulfides, having the second sulfur branching from the first and not partaking in a continuous chain, i.e. >S=S rather than −S−S−.
Compounds with three sulfur atoms, such as CH3S−S−SCH3, are called trisulfides. More extended species are well known, especially in rings.
Disulfide is also used to refer to compounds that contain two sulfide (S2−) centers. The compoundcarbon disulfide, CS2 is described with the structural formula i.e. S=C=S. This molecule is not a disulfide in the sense that it lacks a S-S bond. Similarly,molybdenum disulfide, MoS2, is not a disulfide in the sense again that its sulfur atoms are not linked.
Disulfide bonds are analogous but more common than relatedperoxide,thioselenide, anddiselenide bonds. Intermediate compounds of these also exist, for example thioperoxides such ashydrogen thioperoxide, have the formula R1OSR2 (equivalently R2SOR1). These are isomeric tosulfoxides in a similar manner to the above; i.e. >S=O rather than −S−O−.
The disulfideanion isS2−
2, or−S−S−. In disulfide,sulfur exists in the reduced state with oxidation number −1. Its electron configuration then resembles that of achlorine atom. It thus tends to form a covalent bond with another S− center to formS2−
2 group, similar to elemental chlorine existing as the diatomic Cl2.Oxygen may also behave similarly, e.g. inperoxides such as H2O2. Examples of inorganic disulfides include:
Aside from themajor role in biology, disulfides are found in rubber that has been vulcanized with sulfur. Thevulcanization ofrubber results in crosslinking groups which consist of disulfide (and polysulfide) bonds; in analogy to the role of disulfides in proteins, the S−S linkages in rubber strongly affect the stability andrheology of the material.[14] 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.[14][15] The current conventional methods of rubber manufacturing are typically irreversible, as the unregulated reaction mechanisms can result in complex networks of sulfide linkages; as such, rubber is considered to be athermoset material.[14][16]
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