Misplaced Pages

Cross-link: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively← Previous editContent deleted Content addedVisualWikitext
Revision as of 07:31, 20 September 2013 editKjkolb (talk | contribs)Administrators20,859 edits both "crosslinking agent" and "cross-linking agent" redirect here, other usage: Crosslinking of DNA← Previous edit Latest revision as of 09:34, 27 July 2024 edit undoAlan U. Kennington (talk | contribs)Extended confirmed users1,929 editsm →Research: Split a long paragraph at a logical break. 
(201 intermediate revisions by more than 100 users not shown)
Line 1: Line 1:
{{Short description|Bonds linking one polymer chain to another}}
:''"Reticular" redirects here. For other uses, see ]. For water distribution networks, see ]. "Crosslink" redirects here. For Anglia Railways' train service, see ]. "Crosslinking agent" redirects here. For the crosslinking of DNA, see ].''
{{Hatnote|Several terms redirect here. You may be looking for ], ], or ]; see also ].}}
⚫ ] is an example of cross-linking. Schematic presentation of two "polymer chains" (<span style="color: blue;">'''blue'''</span> and <span style="color: green;">'''green'''</span>) cross-linked after the ] of natural rubber with ] (n = 0, 1, 2, 3 …).
<!--{{Redirect|Reticular}}
{{For2|water distribution networks|]}}
{{Redirect|Crosslink|Anglia Railways' train service|London Crosslink}}
{{Redirect|Crosslinking agent|the occurrence in genetics|Crosslinking of DNA}}-->
⚫ ] is an example of cross-linking. Schematic presentation of two "polymer chains" (<span style="color: blue;">'''blue'''</span> and <span style="color: green;">'''green'''</span>) cross-linked after the ] of natural rubber with ] (n = 0, 1, 2, 3, ...).]]


<!--
{{Quote box {{Quote box
|title = IUPAC definition
|title= ] definition
|quote = A small region in a ] from which at least four chains<br/>emanate, and formed by reactions involving sites or groups on existing<br/>macromolecules or by interactions between existing macromolecules. |quote= A small region in a ] from which at least four chains<br />emanate, and formed by reactions involving sites or groups on existing<br />macromolecules or by interactions between existing macromolecules.


''Notes'' ''Notes''


1. The small region may be an atom, a group of atoms, or a number of<br/>branch points connected by bonds, groups of atoms, or oligomeric chains. 1. The small region may be an atom, a group of atoms, or a number of<br />branch points connected by bonds, groups of atoms, or oligomeric chains.


2. In the majority of cases, a crosslink is a covalent structure but the term<br/>is also used to describe sites of weaker chemical interactions, portions of<br/>crystallites, and even physical interactions and entanglements.<ref>{{cite journal|title=Glossary of basic terms in polymer science (IUPAC Recommendations 1996)|journal=]|year=1996|volume=68|issue=12|pages=2287-2311|doi=10.1351/pac199668122287|url=http://pac.iupac.org/publications/pac/pdf/1996/pdf/6812x2287.pdf}}</ref> 2. In the majority of cases, a crosslink is a covalent structure but the term<br />is also used to describe sites of weaker chemical interactions, portions of<br />crystallites, and even physical interactions and entanglements.<ref>{{cite journal|title=Glossary of basic terms in polymer science (IUPAC Recommendations 1996)|journal=]|year=1996|volume=68|issue=12|pages=2287–2311|quote= 1.59 Crosslink (p.2298)|doi=10.1351/pac199668122287|url=http://www.iupac.org/publications/pac/1996/pdf/6812x2287.pdf |last1= Jenkins |first1= A. D.|s2cid=98774337}}</ref>
}} }}
-->
A '''cross-link''' is a bond that links one ] chain to another. They can be ]s or ]s. "Polymer chains" can refer to synthetic polymers or natural polymers (such as ]s). When the term "cross-linking" is used in the synthetic polymer science field, it usually refers to the use of cross-links to promote a difference 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 ]s, as well as other creative cross-linking methodologies.
]
In ] and ], a '''cross-link''' is a bond or a short sequence of bonds that links one ] chain to another. These links may take the form of ]s or ]s and the polymers can be either synthetic polymers or natural polymers (such as ]s).


In ] "cross-linking" usually refers to the use of cross-links to promote a change in the polymers' physical properties.
⚫ Cross-linking is used in both synthetic polymer chemistry and in the biological sciences. 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. Of course, with all science, there are overlaps, and the following delineations are a starting point to understanding the subtleties.


When "crosslinking" is used in the biological field, it refers to the use of a probe to link proteins together to check for ]s, as well as other creative cross-linking methodologies.{{Not verified in body|date=September 2018}}<!-- probe is used as a verb elsewhere in the article; but not as a noun. Could not find a source to support this statement that the term always refers to use a a probe. -->
When cross links are added to long rubber molecules, the flexibility decreases, the hardness increases and the melting point increases as well.


⚫ 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.
==Cross-links in synthetic polymer chemistry==
When polymer chains are linked together by cross-links, they lose some of their ability to move as individual polymer chains. For example, a liquid polymer (where the chains are freely flowing) can be turned into a "solid" or "gel" by cross-linking the chains together.


==Synthetic polymers==
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 decrease the viscosities of ]. Intermediate cross-link densities transform gummy polymers into materials that have ]ic properties and potentially high strengths. Very high cross-link densities can cause materials to become very rigid or glassy, such as ] materials.<ref></ref>
:]s, the process that produces ].]]
Crosslinking generally involves covalent bonds that join two polymer chains. The term '']'' refers to the crosslinking of ] resins, such as unsaturated ] and ] resin, and the term '']'' is characteristically used for ]s.<ref>{{cite book|author1=Hans Zweifel|author2=Ralph D. Maier|author3=Michael Schiller|title=Plastics additives handbook |date=2009 |publisher=Hanser |location=Munich |isbn=978-3-446-40801-2 |page=746 |edition= 6th}}</ref> When polymer chains are crosslinked, the material becomes more rigid. The mechanical properties of a polymer depend strongly on the cross-link density. Low cross-link densities increase the viscosities of ]s. Intermediate cross-link densities transform gummy polymers into materials that have ]ic properties and potentially high strengths. Very high cross-link densities can cause materials to become very rigid or glassy, such as ] materials.<ref>{{cite book|url=https://books.google.com/books?id=q034u2kLAagC&pg=PA22|title=Engineering with Rubber: How to Design Rubber Components|first=Alan N.|last=Gent|date=1 April 2018|publisher=Hanser|access-date=1 April 2018|via=Google Books|isbn=9781569902998}}</ref>


] derived from ]. Free-radical polymerization gives a highly crosslinked polymer.<ref name="Ullmann">{{cite encyclopedia|last1=Pham|first1=Ha Q.|last2=Marks|first2=Maurice J.|title=Epoxy Resins|encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry|year=2012|doi=10.1002/14356007.a09_547.pub2|isbn=978-3527306732}}</ref>]]
===Formation of cross-links===
Cross-links can be formed by ]s that are initiated by heat, pressure, change in pH, or radiation. For example, mixing of an unpolymerized or partially polymerized ] 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 ] through exposure to a radiation source, such as ] exposure{{Citation needed|date=September 2009}}, gamma-radiation, or UV light. For example, ] is used to cross-link the C type of ]. Other types of cross-linked polyethylene are made by addition of peroxide during ] (type A) or by addition of a cross-linking agent (e.g. ]) and a catalyst during extruding and then performing a post-extrusion curing.


In one implementation, unpolymerized or partially polymerized ] is treated with a '''crosslinking reagent'''. In ], sulfur is the cross-linking agent. Its introduction changes ] to a more rigid, durable material associated with car and bike ]s. This process is often called sulfur curing. In most cases, cross-linking is irreversible, and the resulting thermosetting material will degrade or burn if heated, without melting. Chemical covalent cross-links are stable mechanically and thermally. Therefore, cross-linked products like car ]s cannot be recycled easily.
The chemical process of ] is a type of cross-linking and it changes the property of ] to the hard, durable material we associate with car and bike ]s.
This process is often called sulfur curing, and the term ] comes from ], the ] 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. ] increase the rate of cure by catalysing the addition of sulfur chains to the rubber molecules.


⚫ A class of polymers known as ]s rely on physical cross-links in their microstructure to achieve stability, and are widely used in non-tire applications, such as ] tracks, and ]s 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.
Cross-links are the characteristic property of ] 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. ] solutions, for example, break and re-form naturally occurring cross-links (]s) between protein chains in ].

] is a cross-linking agent: the ] groups link to silica and the ] groups vulcanize with ]s.]]

], the dominant type of commercial oil-based paint, cure by oxidative crosslinking after exposure to air.<ref>{{Citation |last1=Abraham |first1=T.W. |title=Lipid-Based Polymer Building Blocks and Polymers |date=2012 |url=https://linkinghub.elsevier.com/retrieve/pii/B9780444533494002533 |work=Polymer Science: A Comprehensive Reference |pages=15–58 |publisher=Elsevier |language=en |doi=10.1016/b978-0-444-53349-4.00253-3 |isbn=978-0-08-087862-1 |access-date=2022-06-27 |last2=Höfer |first2=R.}}</ref>


===Physical cross-links=== ===Physical cross-links===
In contrast to chemical cross-links, physical cross-links are formed by weaker interactions. For example, sodium ] gels upon exposure to calcium ions, which form ionic bonds that bridge between alginate chains.<ref>{{cite journal |doi= 10.1021/acs.biomac.6b00378|pmid= 27177209|title= Structural Characterization of Sodium Alginate and Calcium Alginate|journal= Biomacromolecules|volume= 17|issue= 6|pages= 2160–2167|year= 2016|last1= Hecht|first1= Hadas|last2= Srebnik|first2= Simcha}}</ref> ] gels upon the addition of ] through hydrogen bonding between ] and the polymer's alcohol groups.<ref>{{cite web |title=Experiments: PVA polymer slime |url=https://edu.rsc.org/experiments/pva-polymer-slime/756.article |website=Education: Inspiring your teaching and learning |publisher=Royal Society of Chemistry |access-date=2 April 2022 |date=2016 |quote=A solution of polyvinyl alcohol (PVA) can be made into a slime by adding borax solution, which creates cross-links between polymer chains.}}</ref><ref>{{cite journal |doi= 10.1021/ed063p57|title= The gelation of polyvinyl alcohol with borax: A novel class participation experiment involving the preparation and properties of a "slime"|journal= Journal of Chemical Education|volume= 63|issue= 1|pages= 57|year= 1986|last1= Casassa|first1= E.Z|last2= Sarquis|first2= A.M|last3= Van Dyke|first3= C.H|bibcode= 1986JChEd..63...57C}}</ref> Other examples of materials which form physically cross-linked gels include ], ], ], and ].
⚫ Chemical covalent cross-links are stable mechanically and thermally, so once formed are difficult to break. Therefore, cross-linked products like car ]s cannot be recycled easily. A class of polymers known as ]s rely on physical cross-links in their microstructure to achieve stability, and are widely used in non-tire applications, such as ] tracks, and ]s 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 stabilising domains may be non-crystalline (as in styrene-butadiene block copolymers) or crystalline as in thermoplastic copolyesters.


==Measuring degree of crosslinking==
===Oxidative cross-links===
Crosslinking is often measured by ] 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.<ref>Flory, P.J., "Principles of Polymer Chemistry" (1953)</ref>
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.


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.<ref>{{cite web|url=http://www.astm.org/Standards/D2765.htm|title=ASTM D2765 - 16 Standard Test Methods for Determination of Gel Content and Swell Ratio of Crosslinked Ethylene Plastics|website=www.astm.org|access-date=1 April 2018}}</ref> 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.<ref>{{cite web|url=http://www.astm.org/Standards/F2214.htm|title=ASTM F2214 - 16 Standard Test Method for In Situ Determination of Network Parameters of Crosslinked Ultra High Molecular Weight Polyethylene (UHMWPE)|website=www.astm.org|access-date=1 April 2018}}</ref> The crosslink density can then be calculated.
⚫ 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 a basic solution of hydrogen peroxide, which causes new disulfide bonds to form under conditions of oxidation, thus permanently fixing the hair into its new configuration.


==In biology==
==Crosslinks in the biological sciences==
]
] naturally present in the body can contain crosslinks generated by ]-catalyzed or spontaneous reactions. Such crosslinks are important in generating mechanically stable structures such as ], ] and ]. ] formation is one of the most common crosslinks, but ] formation is also common. Proteins can also be cross-linked artificially using small-molecule crosslinkers. Compromised ] in the cornea, a condition known as ], can be treated with clinical crosslinking.<ref>Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7.</ref>


===Lignin===
=== Crosslinker use in protein study ===
] is a highly crosslinked polymer that comprises the main structural material of higher plants. A hydrophobic material, it is derived from precursor ]s. Heterogeneity arises from the diversity and degree of crosslinking between these lignols.
The interactions or mere proximity of ]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<ref></ref> could be used to probe the ] between these two proteins by linking them together, disrupting the cell, and looking for the crosslinked proteins.


===In DNA===
A variety of crosslinkers are used to analyze ] structure of ]s, ]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 ]. Protein interactions are often too weak or transient to be easily detected, but, by crosslinking, the interactions can be stabilized, captured, and analyzed.
]), a DNA crosslinker. Like most crosslinkers, this molecule has two reactive groups.]]
Intrastrand ]s have strong effects on organisms because these lesions interfere with ] and ]. These effects can be put to good use (addressing cancer) or they can be lethal to the host organism. The drug ] functions by formation of intrastrand crosslinks in DNA.<ref>{{cite journal |doi=10.1038/sj.onc.1206933 |title=Cisplatin: Mode of cytotoxic action and molecular basis of resistance |date=2003 |last1=Siddik |first1=Zahid H. |journal=Oncogene |volume=22 |issue=47 |pages=7265–7279 |pmid=14576837 |s2cid=4350565 |doi-access=free }}</ref> Other crosslinking agents include ], ], and ].<ref>{{cite journal |doi=10.1021/cr040478b |title=Formation and Repair of Interstrand Cross-Links in DNA |date=2006 |last1=Noll |first1=David M. |last2=Mason |first2=Tracey Mcgregor |last3=Miller |first3=Paul S. |journal=Chemical Reviews |volume=106 |issue=2 |pages=277–301 |pmid=16464006 |pmc=2505341 }}</ref>


===Proteins===
Examples of some common crosslinkers are the ] crosslinker dimethyl suberimidate, the ]-ester crosslinker ] and ]. Each of these crosslinkers induces nucleophilic attack of the amino group of ] and subsequent covalent bonding via the crosslinker. The zero-length ] crosslinker ] 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 ], crosslinks are important in generating mechanically stable structures such as ] and ], ], and ]. ]s are common crosslinks.<ref>{{cite book |doi=10.1002/0471238961.2315151214012107.a01.pub2 |chapter=Wool |title=Kirk-Othmer Encyclopedia of Chemical Technology |date=2005 |last1=Christoe |first1=John R. |last2=Denning |first2=Ron J. |last3=Evans |first3=David J. |last4=Huson |first4=Mickey G. |last5=Jones |first5=Leslie N. |last6=Lamb |first6=Peter R. |last7=Millington |first7=Keith R. |last8=Phillips |first8=David G. |last9=Pierlot |first9=Anthony P. |last10=Rippon |first10=John A. |last11=Russell |first11=Ian M. |isbn=9780471484943 }}</ref> ] formation is another type of protein crosslink.


⚫ The process of applying a ] to hair involves the breaking and reformation of disulfide bonds. Typically a mercaptan such as ammonium thioglycolate is used for the breaking. 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, thus permanently fixing the hair into its new configuration.
''In-vivo'' crosslinking of protein complexes using ]s was introduced in 2005 by researchers from the ].<ref>{{cite journal |last=Suchanek |first=Monika |coauthors=Anna Radzikowska and Christoph Thiele |title=Photo-leucine and photo-methionine allow identification of protein–protein interactions in living cells |journal=Nature Methods |volume=2 |issue=4 |pages=261–268 |year=2005 |month=April |pmid=15782218 |doi= 10.1038/nmeth752|url=http://www.nature.com/nmeth/journal/v2/n4/abs/nmeth752.html |accessdate=2008-07-18}}</ref> In this method, cells are grown with ] ] analogs to ] and ], which are incorporated into proteins. Upon exposure to ultraviolet light, the diazirines are activated and bind to interacting proteins that are within a few ]s of the photo-reactive amino acid analog (UV cross-linking).


Compromised ] in the cornea, a condition known as ], can be treated with clinical crosslinking.<ref>Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7.</ref>
==Uses for crosslinked polymers==
<!--
Synthetically crosslinked polymers have many uses, including those in the biological sciences, such as applications in forming ] gels for ]. Synthetic rubber used for ]s is made by crosslinking rubber through the process of ]. Also most rubber articles are cross-linked to make them more elastic. Hard-shell kayaks are also often manufactured with crosslinked polymers.
It also happens for ] which change structure of foods.
-->
In biological context crosslinking could play a role in ] through ]s (AGEs), which have been implicated to induce crosslinking of collagen, which may lead to vascular stiffening.<ref>{{cite journal|last1=Prasad|first1=Anand|last2=Bekker|first2=Peter|last3=Tsimikas|first3=Sotirios|date=2012-08-01|title=Advanced glycation end products and diabetic cardiovascular disease|journal=Cardiology in Review|volume=20|issue=4|pages=177–183|doi=10.1097/CRD.0b013e318244e57c|issn=1538-4683|pmid=22314141|s2cid=8471652}}</ref>


====Research====
Alkyd enamels, the dominant type of commercial oil-based paint, cure by oxidative crosslinking after exposure to air.
Proteins can also be cross-linked artificially using small-molecule crosslinkers. This approach has been used to elucidate ]s.<ref>{{cite web|url=http://www.piercenet.com/Objects/View.cfm?type=Page&ID=FE7F690D-58AE-4342-AE85-BA94DCA642F8|title=Pierce Protein Biology - Thermo Fisher Scientific|website=www.piercenet.com|access-date=1 April 2018}}</ref><ref name="Kou Qin">{{cite journal |author1=Kou Qin |author2=Chunmin Dong |author3=Guangyu Wu |author4=Nevin A Lambert |date=August 2011 |title= Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers |journal= Nature Chemical Biology |volume= 7 |issue= 11 |pages= 740–747 |doi=10.1038/nchembio.642 |pmid=21873996 |pmc=3177959}}</ref><ref>{{Cite journal|last1=Mizsei|first1=Réka|last2=Li|first2=Xiaolong|last3=Chen|first3=Wan-Na|last4=Szabo|first4=Monika|last5=Wang|first5=Jia-huai|last6=Wagner|first6=Gerhard|last7=Reinherz|first7=Ellis L.|last8=Mallis|first8=Robert J.|date=January 2021|title=A general chemical crosslinking strategy for structural analyses of weakly interacting proteins applied to preTCR-pMHC complexes|journal=Journal of Biological Chemistry|volume=296|pages=100255|doi=10.1016/j.jbc.2021.100255|pmid=33837736|pmc=7948749|issn=0021-9258|doi-access=free}}</ref> Crosslinkers bind only surface residues in relatively close proximity in the ]. Common crosslinkers include the ] crosslinker dimethyl suberimidate, the ]-ester crosslinker ] and ]. Each of these crosslinkers induces nucleophilic attack of the amino group of ] and subsequent covalent bonding via the crosslinker. The zero-length ] crosslinker ] 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.


An ''in-vitro'' cross-linking method is PICUP (]).<ref name=":0">{{cite journal|last1=Fancy|first1=David A.|last2=Kodadek|first2=Thomas|date=1999-05-25|title=Chemistry for the analysis of protein–protein interactions: Rapid and efficient cross-linking triggered by long wavelength light|journal=Proceedings of the National Academy of Sciences|language =en|volume=96|issue=11|pages=6020–6024|doi=10.1073/pnas.96.11.6020|issn=0027-8424|pmid=10339534|pmc=26828|bibcode=1999PNAS...96.6020F|doi-access=free}}</ref> Typical reagents are ] (APS), an electron acceptor, the photosensitizer ] ({{chem2|(2+)}}).<ref name=":0"/> In ''in-vivo'' crosslinking of protein complexes, cells are grown with ] ] analogs to ] and ], which are incorporated into proteins. Upon exposure to ultraviolet light, the diazirines are activated and bind to interacting proteins that are within a few ]s of the photo-reactive amino acid analog (UV cross-linking).<ref>{{cite journal |last=Suchanek |first=Monika |author2=Anna Radzikowska |author3=Christoph Thiele |title=Photo-leucine and photo-methionine allow identification of protein–protein interactions in living cells |journal=Nature Methods |volume=2 |issue=4 |pages=261–268 |date=April 2005 |pmid=15782218 |doi= 10.1038/nmeth752|doi-access=free }}</ref>
Novel uses for crosslinking can be found in regenerative medicine, where bio-scaffolds are crosslinked to improve their mechanical properties.<ref name="Genipin"></ref> More specifically increasing the resistance to dissolution in water based solutions.


== See also == ==See also==
*] *]
*] *]
*] (PEX)
⚫ *] and ]
*Application in enzyme catalysis: ]
*] *]
*] *]
⚫ *] (phenolic resin)


==References== ==References==
⚫ {{Reflist|30em}}
'''Notes'''

⚫ {{Reflist}}
==External links==
* {{Webarchive|url=https://web.archive.org/web/20131102060502/http://www.campoly.com/index.php/download_file/view/380/108/ |date=2013-11-02 }}

{{Authority control}}


]
{{DEFAULTSORT:Cross-Link}}
] ]
] ]
] ]

Latest revision as of 09:34, 27 July 2024

Bonds linking one polymer chain to another Several terms redirect here. You may be looking for Crosslinking of DNA, London Crosslink, or Water management infrastructure; see also Reticular (disambiguation).
Vulcanization is an example of cross-linking. Schematic presentation of two "polymer chains" (blue and green) cross-linked after the vulcanization of natural rubber with sulfur (n = 0, 1, 2, 3, ...).
IUPAC definition for a crosslink in polymer chemistry

In chemistry and biology, a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural polymers (such as proteins).

In polymer chemistry "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.

Synthetic polymers

Chemical reactions associated with crosslinking of drying oils, the process that produces linoleum.

Crosslinking generally involves covalent bonds that join two polymer chains. The term curing refers to the crosslinking of thermosetting resins, such as unsaturated polyester and epoxy resin, and the term vulcanization is characteristically used for rubbers. When polymer chains are crosslinked, the material becomes more rigid. The mechanical properties of a polymer depend strongly on the cross-link density. Low cross-link densities increase the viscosities of polymer melts. Intermediate cross-link densities transform gummy polymers into materials that have elastomeric properties and potentially high strengths. Very high cross-link densities can cause materials to become very rigid or glassy, such as phenol-formaldehyde materials.

Typical vinyl ester resin derived from bisphenol A diglycidyl ether. Free-radical polymerization gives a highly crosslinked polymer.

In one implementation, unpolymerized or partially polymerized resin is treated with a crosslinking reagent. In vulcanization, sulfur is the cross-linking agent. Its introduction changes rubber to a more rigid, durable material associated with car and bike tires. This process is often called sulfur curing. In most cases, cross-linking is irreversible, and the resulting thermosetting material will degrade or burn if heated, without melting. Chemical covalent cross-links are stable mechanically and thermally. Therefore, cross-linked products like car tires 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.

The compound bis(triethoxysilylpropyl)tetrasulfide is a cross-linking agent: the siloxy groups link to silica and the polysulfide groups vulcanize with polyolefins.

Alkyd enamels, the dominant type of commercial oil-based paint, cure by oxidative crosslinking after exposure to air.

Physical cross-links

In contrast to chemical cross-links, physical cross-links are formed by weaker interactions. For example, sodium alginate gels upon exposure to calcium ions, which form ionic bonds that bridge between alginate chains. Polyvinyl alcohol gels upon the addition of borax through hydrogen bonding between boric acid and the polymer's alcohol groups. Other examples of materials which form physically cross-linked gels include gelatin, collagen, agarose, and agar agar.

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.

In biology

Idealized structure of lignin, a highly crosslinked polymer that is the main structural material in many plants.

Lignin

Lignin is a highly crosslinked polymer that comprises the main structural material of higher plants. A hydrophobic material, it is derived from precursor monolignols. Heterogeneity arises from the diversity and degree of crosslinking between these lignols.

In DNA

HN1 (bis(2-chloroethyl)ethylamine), a DNA crosslinker. Like most crosslinkers, this molecule has two reactive groups.

Intrastrand DNA crosslinks have strong effects on organisms because these lesions interfere with transcription and replication. These effects can be put to good use (addressing cancer) or they can be lethal to the host organism. The drug cisplatin functions by formation of intrastrand crosslinks in DNA. Other crosslinking agents include mustard gas, mitomycin, and psoralen.

Proteins

In proteins, crosslinks are important in generating mechanically stable structures such as hair and wool, skin, and cartilage. Disulfide bonds are common crosslinks. Isopeptide bond formation is another type of protein crosslink.

The process of applying a permanent wave to hair involves the breaking and reformation of disulfide bonds. Typically a mercaptan such as ammonium thioglycolate is used for the breaking. 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, thus permanently fixing the hair into its new configuration.

Compromised collagen in the cornea, a condition known as keratoconus, 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.

Research

Proteins can also be cross-linked artificially using small-molecule crosslinkers. This approach has been used to elucidate protein–protein interactions. Crosslinkers bind only surface residues in relatively close proximity in the native state. Common crosslinkers include the imidoester crosslinker dimethyl suberimidate, the N-Hydroxysuccinimide-ester crosslinker BS3 and formaldehyde. Each of these crosslinkers induces nucleophilic attack of the amino group of lysine and subsequent covalent bonding via the crosslinker. The zero-length carbodiimide crosslinker EDC 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.

An in-vitro cross-linking method is PICUP (photo-induced cross-linking of unmodified proteins). Typical reagents are ammonium persulfate (APS), an electron acceptor, the photosensitizer tris-bipyridylruthenium (II) cation ([Ru(bpy)3]). In in-vivo crosslinking of protein complexes, cells are grown with photoreactive diazirine analogs to leucine and methionine, 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).

See also

References

  1. Hans Zweifel; Ralph D. Maier; Michael Schiller (2009). Plastics additives handbook (6th ed.). Munich: Hanser. p. 746. ISBN 978-3-446-40801-2.
  2. Gent, Alan N. (1 April 2018). Engineering with Rubber: How to Design Rubber Components. Hanser. ISBN 9781569902998. Retrieved 1 April 2018 – via Google Books.
  3. Pham, Ha Q.; Marks, Maurice J. (2012). "Epoxy Resins". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a09_547.pub2. ISBN 978-3527306732.
  4. Abraham, T.W.; Höfer, R. (2012), "Lipid-Based Polymer Building Blocks and Polymers", Polymer Science: A Comprehensive Reference, Elsevier, pp. 15–58, doi:10.1016/b978-0-444-53349-4.00253-3, ISBN 978-0-08-087862-1, retrieved 2022-06-27
  5. Hecht, Hadas; Srebnik, Simcha (2016). "Structural Characterization of Sodium Alginate and Calcium Alginate". Biomacromolecules. 17 (6): 2160–2167. doi:10.1021/acs.biomac.6b00378. PMID 27177209.
  6. "Experiments: PVA polymer slime". Education: Inspiring your teaching and learning. Royal Society of Chemistry. 2016. Retrieved 2 April 2022. A solution of polyvinyl alcohol (PVA) can be made into a slime by adding borax solution, which creates cross-links between polymer chains.
  7. Casassa, E.Z; Sarquis, A.M; Van Dyke, C.H (1986). "The gelation of polyvinyl alcohol with borax: A novel class participation experiment involving the preparation and properties of a "slime"". Journal of Chemical Education. 63 (1): 57. Bibcode:1986JChEd..63...57C. doi:10.1021/ed063p57.
  8. Flory, P.J., "Principles of Polymer Chemistry" (1953)
  9. "ASTM D2765 - 16 Standard Test Methods for Determination of Gel Content and Swell Ratio of Crosslinked Ethylene Plastics". www.astm.org. Retrieved 1 April 2018.
  10. "ASTM F2214 - 16 Standard Test Method for In Situ Determination of Network Parameters of Crosslinked Ultra High Molecular Weight Polyethylene (UHMWPE)". www.astm.org. Retrieved 1 April 2018.
  11. Siddik, Zahid H. (2003). "Cisplatin: Mode of cytotoxic action and molecular basis of resistance". Oncogene. 22 (47): 7265–7279. doi:10.1038/sj.onc.1206933. PMID 14576837. S2CID 4350565.
  12. Noll, David M.; Mason, Tracey Mcgregor; Miller, Paul S. (2006). "Formation and Repair of Interstrand Cross-Links in DNA". Chemical Reviews. 106 (2): 277–301. doi:10.1021/cr040478b. PMC 2505341. PMID 16464006.
  13. Christoe, John R.; Denning, Ron J.; Evans, David J.; Huson, Mickey G.; Jones, Leslie N.; Lamb, Peter R.; Millington, Keith R.; Phillips, David G.; Pierlot, Anthony P.; Rippon, John A.; Russell, Ian M. (2005). "Wool". Kirk-Othmer Encyclopedia of Chemical Technology. doi:10.1002/0471238961.2315151214012107.a01.pub2. ISBN 9780471484943.
  14. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7.
  15. Prasad, Anand; Bekker, Peter; Tsimikas, Sotirios (2012-08-01). "Advanced glycation end products and diabetic cardiovascular disease". Cardiology in Review. 20 (4): 177–183. doi:10.1097/CRD.0b013e318244e57c. ISSN 1538-4683. PMID 22314141. S2CID 8471652.
  16. "Pierce Protein Biology - Thermo Fisher Scientific". www.piercenet.com. Retrieved 1 April 2018.
  17. Kou Qin; Chunmin Dong; Guangyu Wu; Nevin A Lambert (August 2011). "Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers". Nature Chemical Biology. 7 (11): 740–747. doi:10.1038/nchembio.642. PMC 3177959. PMID 21873996.
  18. Mizsei, Réka; Li, Xiaolong; Chen, Wan-Na; Szabo, Monika; Wang, Jia-huai; Wagner, Gerhard; Reinherz, Ellis L.; Mallis, Robert J. (January 2021). "A general chemical crosslinking strategy for structural analyses of weakly interacting proteins applied to preTCR-pMHC complexes". Journal of Biological Chemistry. 296: 100255. doi:10.1016/j.jbc.2021.100255. ISSN 0021-9258. PMC 7948749. PMID 33837736.
  19. ^ Fancy, David A.; Kodadek, Thomas (1999-05-25). "Chemistry for the analysis of protein–protein interactions: Rapid and efficient cross-linking triggered by long wavelength light". Proceedings of the National Academy of Sciences. 96 (11): 6020–6024. Bibcode:1999PNAS...96.6020F. doi:10.1073/pnas.96.11.6020. ISSN 0027-8424. PMC 26828. PMID 10339534.
  20. Suchanek, Monika; Anna Radzikowska; Christoph Thiele (April 2005). "Photo-leucine and photo-methionine allow identification of protein–protein interactions in living cells". Nature Methods. 2 (4): 261–268. doi:10.1038/nmeth752. PMID 15782218.

External links

Categories: