Disulfide bond

Disulfide bond

Overview
In chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....

, a disulfide bond (Br.E. disulphide bond) is a covalent bond
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

, usually derived by the coupling of two thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

 group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...

s. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry. In formal terms, the connection is a persulfide, in analogy to its congener
Congener
Congener has several different meanings depending on the field in which it is used. Colloquially, it is used to mean a person or thing like another, in character or action.-Biology:In biology, congeners are organisms within the same genus...

, peroxide
Organic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...

 (R-O-O-R), but this terminology is obscure and is no longer used (except in reference to R-S-S-H or H-S-S-H compounds).

The disulfide bond is strong, with a typical bond dissociation energy
Bond dissociation energy
In chemistry, bond-dissociation energy or D0, is one measure of the bond strength in a chemical bond. It is defined as the standard enthalpy change when a bond is cleaved by homolysis, with reactants and products of the homolysis reaction at 0 K...

 of 60 kcal/mole.
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Encyclopedia
In chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....

, a disulfide bond (Br.E. disulphide bond) is a covalent bond
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

, usually derived by the coupling of two thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

 group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...

s. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry. In formal terms, the connection is a persulfide, in analogy to its congener
Congener
Congener has several different meanings depending on the field in which it is used. Colloquially, it is used to mean a person or thing like another, in character or action.-Biology:In biology, congeners are organisms within the same genus...

, peroxide
Organic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...

 (R-O-O-R), but this terminology is obscure and is no longer used (except in reference to R-S-S-H or H-S-S-H compounds).

Properties


The disulfide bond is strong, with a typical bond dissociation energy
Bond dissociation energy
In chemistry, bond-dissociation energy or D0, is one measure of the bond strength in a chemical bond. It is defined as the standard enthalpy change when a bond is cleaved by homolysis, with reactants and products of the homolysis reaction at 0 K...

 of 60 kcal/mole. Being about 40% weaker than C-C and C-H bonds, the disulfide bond is thus often the "weak link" in many molecules. Furthermore, reflecting the polarizability
Polarizability
Polarizability is the measure of the change in a molecule's electron distribution in response to an applied electric field, which can also be induced by electric interactions with solvents or ionic reagents. It is a property of matter...

 of divalent sulfur, the S-S bond is susceptible to scission by polar reagents, both electrophile
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...

s and especially nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

s:
RS-SR + Nu- → RS-Nu + RS-

The disulfide bond is about 2.05 Å in length, about 0.5 Å longer than a C-C bond. Rotation about the S-S axis is subject to a low barrier. Disulfides show a distinct preference for dihedral angle
Dihedral angle
In geometry, a dihedral or torsion angle is the angle between two planes.The dihedral angle of two planes can be seen by looking at the planes "edge on", i.e., along their line of intersection...

s 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 being diphenyl disulfide
Diphenyl disulfide
Diphenyl disulfide is the chemical compound with the formula [C6H5S]2. This colorless crystalline material is often abbreviated Ph2S2. It is one of the most popular organic disulfides used in organic synthesis...

 and dimethyl disulfide
Dimethyl disulfide
Dimethyl disulfide is an organic chemical compound with the molecular formula CH3SSCH3 which is the simplest disulfide. It is a flammable liquid with an unpleasant odor.DMDS can be produced by the reaction of methanethiol with sulfur:-Uses:...

. When the two R groups are not identical, the compound is said to be an unsymmetric or mixed disulfide.

Although the hydrogenation
Hydrogenation
Hydrogenation, to treat with hydrogen, also a form of chemical reduction, is a chemical reaction between molecular hydrogen and another compound or element, usually in the presence of a catalyst. The process is commonly employed to reduce or saturate organic compounds. Hydrogenation typically...

 of disulfides is usually not practical, the equilibrium constant for the reaction provides a measure of the standard redox potential for disulfides:
RSSR + H2 → 2 RSH

This value is about -250 mV vs NHE (pH = 7). By comparison, the standard reduction potential for ferrodoxins is about -430 mV.

Formation of disulfides


Disulfide bonds are usually formed from the oxidation of sulfhydryl (-SH) groups
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

, especially in biological contexts. The transformation is depicted as follows:
2 RSH → RS-SR + 2 H+ + 2 e-

A variety of oxidants promote this reaction including air and hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

. Such reactions are thought to proceed via sulfenic acid
Sulfenic acid
A sulfenic acid is an organosulfur compound and oxoacid with the general formula RSOH, where R ≠ H. Simple sulfenic acids, such as methanesulfenic acid, CH3SOH, are highly reactive and cannot be isolated in solution. In the gas phase the lifetime of methanesulfenic acid is about one minute...

 intermediates. In the laboratory, iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

 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. Alternatively, disulfide bonds in proteins often formed by thiol-disulfide exchange:
RS-SR + R'SH R'S-SR + RSH

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.

The alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...

 of alkali metal di- and polysulfide
Polysulfide
Polysulfides are a class of chemical compounds containing chains of sulfur atoms. There are two main classes of polysulfides: anions and organic polysulfides. Anions have the general formula Sn2−. These anions are the conjugate bases of the hydrogen polysulfides H2nSn...

s gives disulfides. "Thiokol" polymers arise when sodium 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 disulfides, usually for applications in organic synthesis
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...

. Reagents that deliver the equivalent of "RS+" react with thiols to give asymmetrical disulfides:
RSH + R'SNR"2 → RS-SR' + HNR"2, where R"2N = phthalimido

Scission of disulfides


The most important reaction of disulfide bonds is their cleavage, which occurs via reduction. A variety of reductants can be used. In biochemistry, thiols such as mercaptoethanol (b-ME) or dithiothreitol (DTT)
Dithiothreitol
Dithiothreitol is the common name for a small-molecule redox reagent known as Cleland's reagent. DTT's formula is C4H10O2S2 and the molecular structure of its reduced form is shown at the right; its oxidized form is a disulfide-bonded 6-membered ring . Its name derives from the four-carbon...

 serve as reductants, the thiol reagents are used in excess to drive the equilibrium to the right:
RS-SR + HOCH2CH2SH HOCH2CH2S-SCH2CH2OH + 2 RSH


The reductant Tris(2-carboxyethyl)phosphine (TCEP)
TCEP
TCEP is a reducing agent frequently used in biochemistry and molecular biology applications. It is often prepared and used as a hydrochloride salt with a molecular weight of 286.65 gram/mol...

 is useful, beside being odorless compared to b-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
.

In organic synthesis, hydride agents are typically employed for scission of disulfides, such as sodium borohydride
Sodium borohydride
Sodium borohydride, also known as sodium tetrahydridoborate, is an inorganic compound with the formula NaBH4. This white solid, usually encountered as a powder, is a versatile reducing agent that finds wide application in chemistry, both in the laboratory and on a technical scale. Large amounts are...

. More aggressive, alkali metals will effect this reaction:
RS-SR + 2 Na → 2 NaSR

These reactions are often followed by protonation of the resulting metal thiolate:
NaSR + HCl → HSR + NaCl


Thiol-disulfide exchange is a chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...

 in which a thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

ate group attacks a sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...

 atom
Atom
The atom is a basic unit of matter that consists of a dense central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...

 of a disulfide bond -S-S-. The original disulfide bond is broken, and its other sulfur atom (green atom in Figure 1) is released as a new thiolate, carrying away the negative charge. Meanwhile, a new disulfide bond forms between the attacking thiolate (red atom in Figure 1) and the original sulfur atom (blue atom in Figure 1).

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
PKA
PKA, pKa, or other similar variations may stand for:* pKa, the symbol for the acid dissociation constant at logarithmic scale* Protein kinase A, a class of cAMP-dependent enzymes* Pi Kappa Alpha, the North-American social fraternity...

 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
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

. The rearrangement of disulfide bonds within a protein generally occurs via intra-protein thiol-disulfide exchange reactions; a thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

ate group of a cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

 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
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

 or dithiothreitol
Dithiothreitol
Dithiothreitol is the common name for a small-molecule redox reagent known as Cleland's reagent. DTT's formula is C4H10O2S2 and the molecular structure of its reduced form is shown at the right; its oxidized form is a disulfide-bonded 6-membered ring . Its name derives from the four-carbon...

 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 oxidised. 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
Thioredoxin
Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes. In humans, it is encoded by the TXN gene. Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the...

. This small protein, essential in all known organisms, contains two cysteine amino acid residues in a vicinal
Vicinal
Vicinal may refer to:* Vicinal , stands for any two functional groups bonded to two adjacent atoms.* Vicinal , a word where all letters have alphabetic neighbors....

 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.

Other reactions of disulfides


Many specialized organic reaction
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...

s have been developed for disulfides, again mainly associated with the scission of the S-S bond, which is usually the weakest bond in a molecule. In the Zincke disulfide cleavage reactions, disulfides are cleaved to give the to a sulfenyl halide by reaction with bromine
Bromine
Bromine ") is a chemical element with the symbol Br, an atomic number of 35, and an atomic mass of 79.904. It is in the halogen element group. The element was isolated independently by two chemists, Carl Jacob Löwig and Antoine Jerome Balard, in 1825–1826...

 or chlorine
Chlorine
Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...

.

Occurrence in proteins


Disulfide bonds play an important role in the folding and stability of some proteins, usually proteins secreted to the extracellular medium. Since most cellular compartments are reducing environments, in general, disulfide bonds are unstable in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

, with some exceptions as noted below, unless a sulfhydryl oxidase is present.

Disulfide bonds in proteins are formed between the thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

 groups of cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

 residues. The other sulfur-containing amino acid, methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...

, cannot form disulfide bonds. A disulfide bond is typically denoted by hyphenating the abbreviations for cysteine, e.g., when referring to Ribonuclease A
Ribonuclease A
Ribonuclease A is a pancreatic ribonuclease that cleaves single-stranded RNA. Bovine pancreatic RNase A is one of the classic model systems of protein science.-History:...

 the "Cys26-Cys84 disulfide bond", or the "26-84 disulfide bond", or most simply as "C26-C84" where the disulfide bond is understood and does not need to be mentioned. The prototype of a protein disulfide bond is the two-amino-acid peptide cystine
Cystine
Cystine is a dimeric amino acid formed by the oxidation of two cysteine residues that covalently link to make a disulfide bond. This organosulfur compound has the formula 2. It is a white solid, and melts at 247-249 °C...

, which is composed of two cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

 amino acids joined by a disulfide bond (shown in Figure 2 in its unionized form). The structure of a disulfide bond can be described by its dihedral angle
Dihedral angle
In geometry, a dihedral or torsion angle is the angle between two planes.The dihedral angle of two planes can be seen by looking at the planes "edge on", i.e., along their line of intersection...

 between the atoms, which is usually close to ±90°.

The disulfide bond stabilizes the folded form of a protein in several ways:

1) It holds two portions of the protein together, biasing the protein towards the folded topology. That is, the disulfide bond destabilizes the unfolded form of the protein by lowering its entropy.

2) The disulfide bond may form the nucleus of a hydrophobic core of the folded protein, i.e., local hydrophobic residues may condense around the disulfide bond and onto each other through hydrophobic interactions.

3) Related to #1 and #2, the disulfide bond link two segments of the protein chain, the disulfide bond increases the effective local concentration of protein residues and lowers the effective local concentration of water molecules. Since water molecules attack amide-amide hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...

s and break up secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...

, a disulfide bond stabilizes secondary structure in its vicinity. For example, researchers have identified several pairs of peptides that are unstructured in isolation, but adopt stable secondary and tertiary structure upon forming a disulfide bond between them.

A disulfide species is a particular pairing of cysteines in a disulfide-bonded protein and is usually depicted by listing the disulfide bonds in parentheses, e.g., the "(26-84, 58-110) disulfide species". A disulfide ensemble is a grouping of all disulfide species with the same number of disulfide bonds, and is usually denoted as the 1S ensemble, the 2S ensemble, etc. for disulfide species having one, two, etc. disulfide bonds. Thus, the (26-84) disulfide species belongs to the 1S ensemble, whereas the (26-84, 58-110) species belongs to the 2S ensemble. The single species with no disulfide bonds is usually denoted as R for "fully reduced". Under typical conditions, disulfide reshuffling is much faster than the formation of new disulfide bonds or their reduction; hence, the disulfide species within an ensemble equilibrate more quickly than between ensembles.

The native form of a protein is usually a single disulfide species, although some proteins may cycle between a few disulfide states as part of their function, e.g., thioredoxin
Thioredoxin
Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes. In humans, it is encoded by the TXN gene. Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the...

. In proteins with more than two cysteines, non-native disulfide species may be formed, which are almost always unfolded. As the number of cysteines increases, the number of nonnative species increases factorially. The number of ways of forming p disulfide bonds from n cysteine residues is given by the formula


For example, an eight-cysteine protein such as ribonuclease A
Ribonuclease A
Ribonuclease A is a pancreatic ribonuclease that cleaves single-stranded RNA. Bovine pancreatic RNase A is one of the classic model systems of protein science.-History:...

 has 105 different four-disulfide species, only one of which is the native disulfide species. Isomerases have been identified that catalyze the interconversion of disulfide species, accelerating the formation of the native disulfide species.

Disulfide species that have only native disulfide bonds (but not all of them) are denoted by des followed by the lacking native disulfide bond(s) in square brackets. For example, the des[40-95] disulfide species has all the native disulfide bonds except that between cysteines 40 and 95. Disulfide species that lack one native disulfide bond are frequently folded, in particular, if the missing disulfide bond is exposed to solvent in the folded, native protein.

In order to analyze the structure of proteins, it is often necessary to break disulfide bonds. This reduction of disulfide bonds can be accomplished by treatment with 2-mercaptoethanol
2-Mercaptoethanol
2-Mercaptoethanol is the chemical compound with the formula HOCH2CH2SH. It is a hybrid of ethylene glycol, HOCH2CH2OH, and 1,2-ethanedithiol, HSCH2CH2SH...

, dithiothreitol
Dithiothreitol
Dithiothreitol is the common name for a small-molecule redox reagent known as Cleland's reagent. DTT's formula is C4H10O2S2 and the molecular structure of its reduced form is shown at the right; its oxidized form is a disulfide-bonded 6-membered ring . Its name derives from the four-carbon...

, or tris(2-carboxyethyl)phosphine
TCEP
TCEP is a reducing agent frequently used in biochemistry and molecular biology applications. It is often prepared and used as a hydrochloride salt with a molecular weight of 286.65 gram/mol...

.

In prokaryotes and archaea


Disulfide bonds play an important protective role for bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 as a reversible switch that turns a protein on or off when bacterial cells are exposed to oxidation reactions. Hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

 (H
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...

2O
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

2) in particular could severely damage DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 and kill the bacterium
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 at low concentrations if not for the protective action of the SS-bond. Archaea typically have fewer disulfides than higher organisms.

In eukaryotes


In eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 cells, in general, disulfide bonds are formed in the lumen of the RER (rough endoplasmic reticulum) but not in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

. This is due to the oxidative environment of the ER
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 and the reducing environment of the cytosol (see glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

). Thus disulfide bonds are mostly found in secretory proteins, lysosomal proteins, and the exoplasmic domains of membrane proteins.

Notable exceptions to this rule include a number of cytosolic proteins which have cysteine residues in proximity to each other that function as oxidation sensors; when the reductive potential of the cell fails, they oxidize and trigger cellular response mechanisms. Vaccinia
Vaccinia
Vaccinia virus is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes for approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of...

 virus 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.

Disulfide bonds are also formed within and between protamine
Protamine
Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in spermatozoon than histones, but they must be...

s in the sperm
Sperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...

 chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

 of many mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

ian species.

Disulfides in regulatory proteins


As disulfide bonds can be reversibly reduced and re-oxidized, the redox state of these bonds has evolved into a signaling element. 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. The reductive signaling activity has been shown, thus far, to be carried by the ferredoxin thioredoxin system, channeling electrons from the light reactions of photosystem I
Photosystem I
Photosystem I is the second photosystem in the photosynthetic light reactions of algae, plants, and some bacteria. Photosystem I is so named because it was discovered before photosystem II. Aspects of PS I were discovered in the 1950s, but the significances of these discoveries was not yet known...

 to catalytically reduce disulfides in regulated proteins in a light dependent manner. In this way chloroplasts adjust the activity of key processes such as the Calvin-Benson cycle, starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...

 degradation, ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 production and gene expression according to light intensity.

In hair and feathers


Over 90% of the dry weight of hair
Hair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....

 comprises proteins called keratin
Keratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...

s, 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. Feather
Feather
Feathers are one of the epidermal growths that form the distinctive outer covering, or plumage, on birds and some non-avian theropod dinosaurs. They are considered the most complex integumentary structures found in vertebrates, and indeed a premier example of a complex evolutionary novelty. They...

s have similar keratins and are extremely resistant to protein digestive enzymes. Different parts of the hair and feather have different cysteine levels, leading to harder or softer material. Manipulating disulfide bonds in hair is the basis for the permanent wave
Permanent wave
A permanent wave, commonly called a perm, involves the use of chemicals to break and reform the bonds of the hair. The hair is washed and wrapped on a perm rod and waving lotion is applied with a base. This solution creates a chemical reaction that softens the inner structure of the hair by...

 in hairstyling. Reagents that affect the making and breaking of S-S bonds are key, e.g., ammonium thioglycolate
Ammonium thioglycolate
Ammonium thioglycolate, also known as perm salt, is the chemical compound with the formula HSCH2CO2NH4.Being the salt of a weak acid and weak base, ammonium thioglycolic acid exists in solution as an equilibrium mixture of the salt itself as well as the free carboxylic acid thioglycolic acid and...

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

In industry


Disulfide and (polysulfide) bonds are the crosslinking groups that result from the vulcanization
Vulcanization
Vulcanization or vulcanisation is a chemical process for converting rubber or related polymers into more durable materials via the addition of sulfur or other equivalent "curatives." These additives modify the polymer by forming crosslinks between individual polymer chains. Vulcanized material is...

 of rubber
Rubber
Natural rubber, also called India rubber or caoutchouc, is an elastomer that was originally derived from latex, a milky colloid produced by some plants. The plants would be ‘tapped’, that is, an incision made into the bark of the tree and the sticky, milk colored latex sap collected and refined...

. In analogy to the role of disulfides in proteins, the S-S linkages in rubber are crosslinkers, and strongly affect the rheology
Rheology
Rheology is the study of the flow of matter, primarily in the liquid state, but also as 'soft solids' or solids under conditions in which they respond with plastic flow rather than deforming elastically in response to an applied force....

 of the material.

Related compounds


Thiosulfoxide
Thiosulfoxide
A thiosulfoxide is a chemical compound containing a sulfur to sulfur double bond of the type RR'S=S with R and R' both alkyl or aryl residues. A 1982 review concluded that there was as yet no definitive evidence for the existence of stable thiosulfoxides which can be attributed to the double bond...

s are orthogonally 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-.

Disulfide bonds are analogous but more common than related peroxide
Peroxide
A peroxide is a compound containing an oxygen–oxygen single bond or the peroxide anion .The O−O group is called the peroxide group or peroxo group. In contrast to oxide ions, the oxygen atoms in the peroxide ion have an oxidation state of −1.The simplest stable peroxide is hydrogen peroxide...

s and diselenide bonds. Intermediate compounds of these also exist, for example, thioperoxides, also known as oxadisulfide bonds, have formula R1OSR2 (equivalently R2SOR1). These are isomeric to sulfoxide
Sulfoxide
A sulfoxide is a chemical compound containing a sulfinyl functional group attached to two carbon atoms. Sulfoxides can be considered as oxidized sulfides...

s in a similar manner to the above; i.e. -S(=O)- rather than -S-O-.

Thiuram disulfide
Thiuram disulfide
Thiuram disulfides are a class of organic disulfides that have the general structural formula shown to the right.-Preparation:They are prepared from the oxidation of their corresponding sodium salts of thiocarbamates with iodine:-Example:...

s, with the formula (R2NC(S)S)2, are disulfides but they behave distinctly because of the thiocarbonyl group.

Compounds with three sulfur atoms, e.g., CH3S-S-SCH3, are called trisulfides, or trisulfide bonds.

External links