![Vulcanization of POLYIsoprene V](https://upload.wikimedia.org/wikipedia/commons/b/bc/Vulcanization_of_POLYIsoprene_V.2.png)
In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
chain to another. These links may take the form of
covalent bond
A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...
s or
ionic bonds and the polymers can be either synthetic polymers or natural polymers (such as
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s).
In
polymer chemistry
Polymer chemistry is a sub-discipline of chemistry that focuses on the structures of chemicals, chemical synthesis, and chemical and physical properties of polymers and macromolecules. The principles and methods used within polymer chemistry are ...
"cross-linking" usually refers to the use of cross-links to promote a change in the polymers' physical properties.
When "crosslinking" is used in the biological field, it refers to the use of a probe to link proteins together to check for
protein–protein interactions, as well as other creative cross-linking methodologies.
Although the term is used to refer to the "linking of polymer chains" for both sciences, the extent of crosslinking and specificities of the crosslinking agents vary greatly. As with all science, there are overlaps, and the following delineations are a starting point to understanding the subtleties.
Polymer chemistry
Crosslinking is the general term for the process of forming covalent bonds or relatively short sequences of chemical bonds to join two polymer chains together. The term ''
curing'' refers to the crosslinking of
thermosetting resins, such as unsaturated
polyester
Polyester is a category of polymers that contain the ester functional group in every repeat unit of their main chain. As a specific material, it most commonly refers to a type called polyethylene terephthalate (PET). Polyesters include natural ...
and
epoxy
Epoxy is the family of basic components or cured end products of epoxy resins. Epoxy resins, also known as polyepoxides, are a class of reactive prepolymers and polymers which contain epoxide groups. The epoxide functional group is also coll ...
resin, and the term ''
vulcanization'' is characteristically used for
rubber
Rubber, also called India rubber, latex, Amazonian rubber, ''caucho'', or ''caoutchouc'', as initially produced, consists of polymers of the organic compound isoprene, with minor impurities of other organic compounds. Thailand, Malaysia, and ...
s. When polymer chains are crosslinked, the material becomes more rigid.
In polymer chemistry, when a synthetic polymer is said to be "cross-linked", it usually means that the entire bulk of the polymer has been exposed to the cross-linking method. The resulting modification of mechanical properties depends strongly on the cross-link density. Low cross-link densities increase the viscosities of
polymer melt
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic an ...
s. Intermediate cross-link densities transform gummy polymers into materials that have
elastomer
An elastomer is a polymer with viscoelasticity (i.e. both viscosity and elasticity) and with weak intermolecular forces, generally low Young's modulus and high failure strain compared with other materials. The term, a portmanteau of ''elastic p ...
ic properties and potentially high strengths. Very high cross-link densities can cause materials to become very rigid or glassy, such as
phenol-formaldehyde materials.
Formation
Cross-links can be formed by
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
s that are initiated by heat, pressure, change in pH, or
irradiation. For example, mixing of an unpolymerized or partially polymerized
resin
In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on natu ...
with specific chemicals called crosslinking reagents results in a chemical reaction that forms cross-links. Cross-linking can also be induced in materials that are normally
thermoplastic
A thermoplastic, or thermosoft plastic, is any plastic polymer material that becomes pliable or moldable at a certain elevated temperature and solidifies upon cooling.
Most thermoplastics have a high molecular weight. The polymer chains associate ...
through exposure to a radiation source, such as
electron beam
Cathode rays or electron beam (e-beam) are streams of electrons observed in discharge tubes. If an evacuated glass tube is equipped with two electrodes and a voltage is applied, glass behind the positive electrode is observed to glow, due to ele ...
exposure,
gamma radiation
A gamma ray, also known as gamma radiation (symbol γ or \gamma), is a penetrating form of electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves, typically s ...
, or
UV light. For example,
electron beam processing is used to cross-link the C type of
cross-linked polyethylene. Other types of cross-linked polyethylene are made by addition of peroxide during
extruding
Extrusion is a process used to create objects of a fixed cross-sectional profile by pushing material through a die of the desired cross-section. Its two main advantages over other manufacturing processes are its ability to create very complex ...
(type A) or by addition of a cross-linking agent (e.g.
vinylsilane
Vinylsilane refers to an organosilicon compound with chemical formula CH2=CHSiH3. It is a derivative of silane (SiH4). The compound, which is a colorless gas, is mainly of theoretical interest.
Substituted vinylsilanes
More commonly used than th ...
) and a catalyst during extruding and then performing a post-extrusion curing.
The chemical process of
vulcanization is a type of cross-linking that changes
rubber
Rubber, also called India rubber, latex, Amazonian rubber, ''caucho'', or ''caoutchouc'', as initially produced, consists of polymers of the organic compound isoprene, with minor impurities of other organic compounds. Thailand, Malaysia, and ...
to the hard, durable material associated with car and bike
tire
A tire (American English) or tyre (British English) is a ring-shaped component that surrounds a Rim (wheel), wheel's rim to transfer a vehicle's load from the axle through the wheel to the ground and to provide Traction (engineering), t ...
s. This process is often called sulfur curing; the term
vulcanization comes from
Vulcan
Vulcan may refer to:
Mythology
* Vulcan (mythology), the god of fire, volcanoes, metalworking, and the forge in Roman mythology
Arts, entertainment and media Film and television
* Vulcan (''Star Trek''), name of a fictional race and their home p ...
, the
Roman
Roman or Romans most often refers to:
*Rome, the capital city of Italy
*Ancient Rome, Roman civilization from 8th century BC to 5th century AD
*Roman people, the people of ancient Rome
*''Epistle to the Romans'', shortened to ''Romans'', a letter ...
god of fire. This is, however, a slower process. A typical car tire is cured for 15 minutes at 150 °C. However, the time can be reduced by the addition of accelerators such as 2-benzothiazolethiol or tetramethylthiuram disulfide. Both of these contain a sulfur atom in the molecule that initiates the reaction of the sulfur chains with the rubber.
Accelerators increase the rate of cure by catalysing the addition of sulfur chains to the rubber molecules.
Cross-links are the characteristic property of
thermosetting plastic
In materials science, a thermosetting polymer, often called a thermoset, is a polymer that is obtained by irreversibly hardening (" curing") a soft solid or viscous liquid prepolymer (resin). Curing is induced by heat or suitable radiation and ...
materials. In most cases, cross-linking is irreversible, and the resulting thermosetting material will degrade or burn if heated, without melting. Especially in the case of commercially used plastics, once a substance is cross-linked, the product is very hard or impossible to recycle. In some cases, though, if the cross-link bonds are sufficiently different, chemically, from the bonds forming the polymers, the process can be reversed.
Permanent wave
A permanent wave, commonly called a perm or permanent (sometimes called a "curly perm" to distinguish it from a " straight perm"), is a hairstyle consisting of waves or curls set into the hair. The curls may last a number of months, hence the ...
solutions, for example, break and re-form naturally occurring cross-links (
disulfide bonds) between protein chains in
hair
Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals.
The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and f ...
.
Physical cross-links
Where chemical cross-links are covalent bonds, physical cross-links are formed by weak interactions. For example, sodium
alginate gels upon exposure to calcium ion, which allows it to form ionic bonds that bridge between alginate chains.
Polyvinyl alcohol
Poly(vinyl alcohol) (PVOH, PVA, or PVAl) is a water-soluble synthetic polymer. It has the idealized formula H2CH(OH)sub>''n''. It is used in papermaking, textile warp sizing, as a thickener and emulsion stabilizer in polyvinyl acetate (PVAc) a ...
gels upon the addition of
borax
Borax is a salt (ionic compound), a hydrated borate of sodium, with chemical formula often written . It is a colorless crystalline solid, that dissolves in water to make a basic solution. It is commonly available in powder or granular form, ...
through hydrogen bonding between
boric acid and the polymer's alcohol groups. Other examples of materials which form physically cross-linked gels include
gelatin
Gelatin or gelatine (from la, gelatus meaning "stiff" or "frozen") is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also ...
,
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
,
agarose, and
agar agar
Agar ( or ), or agar-agar, is a jelly-like substance consisting of polysaccharides obtained from the cell walls of some species of red algae, primarily from ogonori (''Gracilaria'') and "tengusa" (''Gelidiaceae''). As found in nature, agar is ...
.
Chemical covalent cross-links are stable mechanically and thermally, so once formed are difficult to break. Therefore, cross-linked products like car
tire
A tire (American English) or tyre (British English) is a ring-shaped component that surrounds a Rim (wheel), wheel's rim to transfer a vehicle's load from the axle through the wheel to the ground and to provide Traction (engineering), t ...
s cannot be recycled easily. A class of polymers known as
thermoplastic elastomers rely on physical cross-links in their microstructure to achieve stability, and are widely used in non-tire applications, such as
snowmobile tracks, and
catheters for medical use. They offer a much wider range of properties than conventional cross-linked elastomers because the domains that act as cross-links are reversible, so can be reformed by heat. The stabilizing domains may be non-crystalline (as in styrene-butadiene block copolymers) or crystalline as in thermoplastic copolyesters.
![Si69](https://upload.wikimedia.org/wikipedia/commons/c/c9/Si69.svg)
Note: A rubber which cannot be reformed by heat or chemical treatment is called a thermoset elastomer. On the other hand, a thermoplastic elastomer can be molded and recycled by heat.
Oxidative cross-links
Many polymers undergo oxidative cross-linking, typically when exposed to atmospheric oxygen. In some cases this is undesirable and thus polymerization reactions may involve the use of an antioxidant to slow the formation of oxidative cross-links. In other cases, when formation of cross-links by oxidation is desirable, an oxidizer such as hydrogen peroxide may be used to speed up the process.
The aforementioned process of applying a permanent wave to hair is one example of oxidative cross-linking. In that process the disulfide bonds are reduced, typically using a mercaptan such as ammonium thioglycolate. Following this, the hair is curled and then "neutralized". The neutralizer is typically an acidic solution of hydrogen peroxide, which causes new disulfide bonds to form under conditions of oxidation, thus permanently fixing the hair into its new configuration.
It also happens for
gluten which change structure of foods.
In biology
Proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
naturally present in the body can contain crosslinks generated by
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
-catalyzed or spontaneous reactions. Such crosslinks are important in generating mechanically stable structures such as
hair
Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals.
The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and f ...
,
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
, and
cartilage
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
.
Disulfide bond formation is one of the most common crosslinks, but
isopeptide bond formation is also common. Proteins can also be cross-linked artificially using small-molecule crosslinkers. Compromised
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
in the cornea, a condition known as
keratoconus
Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. Usu ...
, can be treated with clinical crosslinking.
In biological context crosslinking could play a role in
atherosclerosis through
advanced glycation end-products (AGEs), which have been implicated to induce crosslinking of collagen, which may lead to vascular stiffening.
Use in protein study
The interactions or mere proximity of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s can be studied by the clever use of crosslinking agents. For example, protein A and protein B may be very close to each other in a cell, and a chemical crosslinker could be used to probe the
protein–protein interaction between these two proteins by linking them together, disrupting the cell, and looking for the crosslinked proteins.
A variety of crosslinkers are used to analyze
subunit
Subunit may refer to:
*Subunit HIV vaccine, a class of HIV vaccine
*Protein subunit, a protein molecule that assembles with other protein molecules
*Monomer, a molecule that may bind chemically to other molecules to form a polymer
*Sub-subunit, a ...
structure of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s,
protein interaction
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s, and various parameters of protein function by using differing crosslinkers, often with diverse spacer arm lengths. Subunit structure is deduced, since crosslinkers bind only surface residues in relatively close proximity in the
native state
In biochemistry, the native state of a protein or nucleic acid is its properly folded and/or assembled form, which is operative and functional. The native state of a biomolecule may possess all four levels of biomolecular structure, with the s ...
. Protein interactions are often too weak or transient to be easily detected, but by crosslinking, the interactions can be stabilized, captured, and analyzed.
Examples of some common crosslinkers are the
imidoester
Carboximidates (or more general imidates) are organic compounds, which can be thought of as esters formed between a carboximidic acid (R-C(=NR')OH) and an alcohol, with the general formula R-C(=NR')OR".
They are also known as imino ethers, si ...
crosslinker dimethyl suberimidate, the
N-Hydroxysuccinimide-ester crosslinker
BS3 BS3 or BS-3 may refer to :
* BS3, a BS postcode area for Bristol, England
* BS3, a Drill bit sizes#Center drill bit sizes, center drill bit size
* 100 mm field gun M1944 (BS-3), a 1944 Soviet gun
* BisSulfosuccinimidyl suberate, a crosslinker used i ...
and
formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
. Each of these crosslinkers induces nucleophilic attack of the amino group of
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
and subsequent covalent bonding via the crosslinker. The zero-length
carbodiimide crosslinker
EDC
EDC or EdC may refer to:
Education
* East Devon College, in Tiverton, Devon, England
* EDC Paris Business School, a French business school
* Education Development Center, an American educational organization
* Department for Education (Sout ...
functions by converting carboxyls into amine-reactive isourea intermediates that bind to lysine residues or other available primary amines. SMCC or its water-soluble analog, Sulfo-SMCC, is commonly used to prepare antibody-hapten conjugates for antibody development.
''In-vitro'' cross-linking method, termed PICUP (
photo-induced cross-linking of unmodified proteins), was developed in 1999.
They devised a process in which
ammonium persulfate (APS), which acts as an electron acceptor, and tris(bipyridine)ruthenium(II) chloride, tris-bipyridylruthenium (II) cation () are added to the protein of interest and irradiated with UV light.
PICUP is more expeditious and high yielding compared to previous chemical cross-linking methods.
''In-vivo'' crosslinking of protein complexes using photo-reactive amino acid analogs was introduced in 2005 by researchers from the Max Planck Institute of Molecular Cell Biology and Genetics. In this method, cells are grown with photoreactive diazirine analogs to leucine and
methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
, which are incorporated into proteins. Upon exposure to ultraviolet light, the diazirines are activated and bind to interacting proteins that are within a few
ångströms of the photo-reactive amino acid analog (UV cross-linking).
In material science
Wide usage of the term cross-linking is also described as vulcanization in material science and engineering, mainly addressing the fast reaction between monomers and polymers and branches of rubber. Cross-linking or interlinking m of polymers can improve the mechanical properties of the polymeric material and also can improve the adhesion between two interfaces of the coating.
Promote the mechanical properties of material
Cross-linked polymers, monomers, and branches can improve the bulk mechanical properties of the material and mostly decrease the viscosity of non-solid materials.
The earliest examples of crosslinking, linking long chains of polymers together to increase strength and mass, involved tires. Rubber was vulcanized with sulfur under heat, which created a link between latex models.
Synthetically crosslinked polymers have many uses, including those in the biological sciences, such as applications in forming
polyacrylamide
Polyacrylamide (abbreviated as PAM) is a polymer with the formula (-CH2CHCONH2-). It has a linear-chain structure. PAM is highly water-absorbent, forming a soft gel when hydrated. In 2008, an estimated 750,000,000 kg were produced, mainly fo ...
gels for
gel electrophoresis
Gel electrophoresis is a method for separation and analysis of biomacromolecules ( DNA, RNA, proteins, etc.) and their fragments, based on their size and charge. It is used in clinical chemistry to separate proteins by charge or size (IEF ...
. Synthetic rubber used for
tire
A tire (American English) or tyre (British English) is a ring-shaped component that surrounds a Rim (wheel), wheel's rim to transfer a vehicle's load from the axle through the wheel to the ground and to provide Traction (engineering), t ...
s is made by crosslinking rubber through the process of
vulcanization. This crosslinking makes them more elastic. Hard-shell kayaks are also often manufactured with crosslinked polymers.
In many hydraulic fracturing treatments, a delayed gel-cross-linker fluid is used to carry out fracture treatment of the rock.
Promote the adhesion of coatings
Two interlinked layers of the interface can increase the adhesion strength of the coating to the surface.
Other examples of polymers that can be crosslinked are
ethylene-vinyl acetate
Ethylene-vinyl acetate (EVA), also known as poly (ethylene-vinyl acetate) (PEVA), is the copolymer of ethylene and vinyl acetate. The weight percent of vinyl acetate usually varies from 10 to 40%, with the remainder being ethylene. There are th ...
– as used in
solar panel
A solar cell panel, solar electric panel, photo-voltaic (PV) module, PV panel or solar panel is an assembly of photovoltaic solar cells mounted in a (usually rectangular) frame, and a neatly organised collection of PV panels is called a photo ...
manufacturing – and
polyethylene
Polyethylene or polythene (abbreviated PE; IUPAC name polyethene or poly(methylene)) is the most commonly produced plastic. It is a polymer, primarily used for packaging ( plastic bags, plastic films, geomembranes and containers including bo ...
.
Alkyd enamels, the dominant type of commercial oil-based paint, cure by oxidative crosslinking after exposure to air.
Measuring degree of crosslinking
Crosslinking is often measured by
swelling tests. The crosslinked sample is placed into a good solvent at a specific temperature, and either the change in mass or the change in volume is measured. The more crosslinking, the less swelling is attainable. Based on the degree of swelling, the Flory Interaction Parameter (which relates the solvent interaction with the sample), and the density of the solvent, the theoretical degree of crosslinking can be calculated according to Flory's Network Theory. Two ASTM standards are commonly used to describe the degree of crosslinking in thermoplastics. In ASTM D2765, the sample is weighed, then placed in a solvent for 24 hours, weighed again while swollen, then dried and weighed a final time. The degree of swelling and the soluble portion can be calculated. In another ASTM standard, F2214, the sample is placed in an instrument that measures the height change in the sample, allowing the user to measure the volume change.
The crosslink density can then be calculated.
See also
*
Branching (polymer chemistry)
In polymer chemistry, branching is the regular or irregular attachment of side chains to a polymer's backbone chain. It occurs by the replacement of a substituent (e.g. a hydrogen atom) on a monomer subunit by another covalently-bonded chai ...
*
Cross-linked enzyme aggregate In biochemistry, a cross-linked enzyme aggregate is an immobilized enzyme prepared via cross-linking of the physical enzyme aggregates with a difunctional cross-linker. They can be used as stereoselective industrial biocatalysts.
Background
Enzymes ...
*
Cross-linked polyethylene (PEX)
*
Crosslinking of DNA
In genetics, crosslinking of DNA occurs when various exogenous or endogenous agents react with two nucleotides of DNA, forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or between opposite stra ...
*
Fixation (histology)
In the fields of histology, pathology, and cell biology, fixation is the preservation of biological tissues from decay due to autolysis or putrefaction. It terminates any ongoing biochemical reactions and may also increase the treated tissues' mec ...
*
Phenol formaldehyde resin (phenolic resin)
References
{{Reflist, 30em
External links
Application note on how to measure degree of crosslinking in plastics
Ageing processes
Polymer chemistry
Protein–protein interaction assays
Rubber properties