N-Hydroxysuccinimide

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N-Hydroxysuccinimide
N-Hydroxysuccinimide.png
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N-Hydroxysuccinimide powder.jpg
Names
Preferred IUPAC name
1-Hydroxypyrrolidine-2,5-dione
Other names
HOSu, HSI.
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.025.456 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C4H5NO3/c6-3-1-2-4(7)5(3)8/h8H,1-2H2 X mark.svgN
    Key: NQTADLQHYWFPDB-UHFFFAOYSA-N X mark.svgN
  • InChI=1/C4H5NO3/c6-3-1-2-4(7)5(3)8/h8H,1-2H2
    Key: NQTADLQHYWFPDB-UHFFFAOYAM
  • O=C1N(O)C(=O)CC1
Properties
C4H5NO3
Molar mass 115.09 g/mol
AppearanceColourless solid
Melting point 96.3 °C (205.3 °F; 369.4 K) [1]
Related compounds
Related imides
Succinimide
N-Bromosuccinimide
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

N-Hydroxysuccinimide (NHS) is an organic compound with the formula (CH2CO)2NOH. It is a white solid that is used as a reagent for preparing active esters in peptide synthesis. It can be synthesized by heating succinic anhydride with hydroxylamine or hydroxylamine hydrochloride. [2]

Contents

Activating reagent

NHS is commonly found in organic chemistry or biochemistry where it is used as an activating reagent for carboxylic acids. [3] Activated acids (carboxylates) can react with amines to form amides for example, whereas a normal carboxylic acid would just form a salt with an amine.

Use

A common way to synthesize an NHS-activated acid is to mix NHS with the desired carboxylic acid and a small amount of an organic base in an anhydrous solvent. A coupling reagent such as dicyclohexylcarbodiimide (DCC) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) is then added to form a highly reactive activated acid intermediate. NHS reacts to create a less labile activated acid. The group is usually written as SuO- or -OSu in chemical notation. Such an ester with acid and NHS, sometimes called succinate ester, is stable enough to be purified and stored at low temperatures in the absence of water and, as such, is commercially available. NHS esters are commonly used for protein modification (e.g. an NHS ester of fluorescein is commercially available, and can be added to a protein to obtain a fluorescently labeled protein in a straightforward reaction and purification step).

NHS can be used with EDC to immobilize enzymes for biosensor applications. [4]

Alternatives

Some alternatives to NHS are the water-soluble analog sulfo-NHS, hydroxybenzotriazole (HOBt), 1-hydroxy-7-azabenzotriazole (HOAt), and pentafluorophenol.

Related Research Articles

<span class="mw-page-title-main">Amide</span> Organic compounds of the form RC(=O)NR′R″

In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula R−C(=O)−NR′R″, where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, such as in the amino acids asparagine and glutamine. It can be viewed as a derivative of a carboxylic acid with the hydroxyl group replaced by an amine group ; or, equivalently, an acyl (alkanoyl) group joined to an amine group.

<span class="mw-page-title-main">Carboxylic acid</span> Organic compound containing a –C(=O)OH group

In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group attached to an R-group. The general formula of a carboxylic acid is often written as R−COOH or R−CO2H, sometimes as R−C(O)OH with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion.

<span class="mw-page-title-main">Ester</span> Compound derived from an acid

In chemistry, an ester is a compound derived from an acid in which the hydrogen atom (H) of at least one acidic hydroxyl group of that acid is replaced by an organyl group. Analogues derived from oxygen replaced by other chalcogens belong to the ester category as well. According to some authors, organyl derivatives of acidic hydrogen of other acids are esters as well, but not according to the IUPAC.

<span class="mw-page-title-main">Hydroxylamine</span> Inorganic compound

Hydroxylamine is an inorganic compound with the formula NH2OH. The material is a white crystalline, hygroscopic compound. Hydroxylamine is almost always provided and used as an aqueous solution. It is consumed almost exclusively to produce Nylon-6. The oxidation of NH3 to hydroxylamine is a step in biological nitrification.

In organic chemistry, an acyl chloride is an organic compound with the functional group −C(=O)Cl. Their formula is usually written R−COCl, where R is a side chain. They are reactive derivatives of carboxylic acids. A specific example of an acyl chloride is acetyl chloride, CH3COCl. Acyl chlorides are the most important subset of acyl halides.

<span class="mw-page-title-main">Dipeptide</span> Shortest peptide molecule, containing two amino acids joined by a single peptide bond

A dipeptide is an organic compound derived from two amino acids. The constituent amino acids can be the same or different. When different, two isomers of the dipeptide are possible, depending on the sequence. Several dipeptides are physiologically important, and some are both physiologically and commercially significant. A well known dipeptide is aspartame, an artificial sweetener.

In biochemistry, biotinylation is the process of covalently attaching biotin to a protein, nucleic acid or other molecule. Biotinylation is rapid, specific and is unlikely to disturb the natural function of the molecule due to the small size of biotin. Biotin binds to streptavidin and avidin with an extremely high affinity, fast on-rate, and high specificity, and these interactions are exploited in many areas of biotechnology to isolate biotinylated molecules of interest. Biotin-binding to streptavidin and avidin is resistant to extremes of heat, pH and proteolysis, making capture of biotinylated molecules possible in a wide variety of environments. Also, multiple biotin molecules can be conjugated to a protein of interest, which allows binding of multiple streptavidin, avidin or neutravidin protein molecules and increases the sensitivity of detection of the protein of interest. There is a large number of biotinylation reagents available that exploit the wide range of possible labelling methods. Due to the strong affinity between biotin and streptavidin, the purification of biotinylated proteins has been a widely used approach to identify protein-protein interactions and post-translational events such as ubiquitylation in molecular biology.

<span class="mw-page-title-main">Peptide synthesis</span> Production of peptides

In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl group of one amino acid to the amino group of another. Protecting group strategies are usually necessary to prevent undesirable side reactions with the various amino acid side chains. Chemical peptide synthesis most commonly starts at the carboxyl end of the peptide (C-terminus), and proceeds toward the amino-terminus (N-terminus). Protein biosynthesis in living organisms occurs in the opposite direction.

<span class="mw-page-title-main">Carbodiimide</span> Class of organic compounds with general structure RN=C=NR

In organic chemistry, a carbodiimide is a functional group with the formula RN=C=NR. On Earth they are exclusively synthetic, but in interstellar space the parent compound HN=C=NH has been detected by its maser emissions.

<span class="mw-page-title-main">Carbonyldiimidazole</span> Chemical compound

1,1'-Carbonyldiimidazole (CDI) is an organic compound with the molecular formula (C3H3N2)2CO. It is a white crystalline solid. It is often used for the coupling of amino acids for peptide synthesis and as a reagent in organic synthesis.

Nucleophilic acyl substitution describes a class of substitution reactions involving nucleophiles and acyl compounds. In this type of reaction, a nucleophile – such as an alcohol, amine, or enolate – displaces the leaving group of an acyl derivative – such as an acid halide, anhydride, or ester. The resulting product is a carbonyl-containing compound in which the nucleophile has taken the place of the leaving group present in the original acyl derivative. Because acyl derivatives react with a wide variety of nucleophiles, and because the product can depend on the particular type of acyl derivative and nucleophile involved, nucleophilic acyl substitution reactions can be used to synthesize a variety of different products.

Cyanogen bromide is the inorganic compound with the formula (CN)Br or BrCN. It is a colorless solid that is widely used to modify biopolymers, fragment proteins and peptides, and synthesize other compounds. The compound is classified as a pseudohalogen.

The Weinreb ketone synthesis or Weinreb–Nahm ketone synthesis is a chemical reaction used in organic chemistry to make carbon–carbon bonds. It was discovered in 1981 by Steven M. Weinreb and Steven Nahm as a method to synthesize ketones. The original reaction involved two subsequent nucleophilic acyl substitutions: the conversion of an acid chloride with N,O-Dimethylhydroxylamine, to form a Weinreb–Nahm amide, and subsequent treatment of this species with an organometallic reagent such as a Grignard reagent or organolithium reagent. Nahm and Weinreb also reported the synthesis of aldehydes by reduction of the amide with an excess of lithium aluminum hydride.

In chemistry, aminolysis (/am·i·nol·y·sis/) is any chemical reaction in which a molecule is lysed by reacting with ammonia or an amine. The case where the reaction involves ammonia may be more specifically referred to as ammonolysis.

<span class="mw-page-title-main">Hydroxybenzotriazole</span> Chemical compound

Hydroxybenzotriazole is an organic compound that is a derivative of benzotriazole. It is a white crystalline powder, which as a commercial product contains some water. Anhydrous HOBt is explosive.

The Stieglitz rearrangement is a rearrangement reaction in organic chemistry which is named after the American chemist Julius Stieglitz (1867–1937) and was first investigated by him and Paul Nicholas Leech in 1913. It describes the 1,2-rearrangement of trityl amine derivatives to triaryl imines. It is comparable to a Beckmann rearrangement which also involves a substitution at a nitrogen atom through a carbon to nitrogen shift. As an example, triaryl hydroxylamines can undergo a Stieglitz rearrangement by dehydration and the shift of a phenyl group after activation with phosphorus pentachloride to yield the respective triaryl imine, a Schiff base.

<span class="mw-page-title-main">1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide</span> Chemical compound

1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide is a water-soluble carbodiimide usually handled as the hydrochloride.

<span class="mw-page-title-main">Trichloroacetonitrile</span> Chemical compound

Trichloroacetonitrile is an organic compound with the formula CCl3CN. It is a colourless liquid, although commercial samples often are brownish. It is used commercially as a precursor to the fungicide etridiazole. It is prepared by dehydration of trichloroacetamide. As a bifunctional compound, trichloroacetonitrile can react at both the trichloromethyl and the nitrile group. The electron-withdrawing effect of the trichloromethyl group activates the nitrile group for nucleophilic additions. The high reactivity makes trichloroacetonitrile a versatile reagent, but also causes its susceptibility towards hydrolysis.

<i>N</i>-Hydroxyphthalimide Chemical compound

N-Hydroxyphthalimide is the N-hydroxy derivative of phthalimide. The compound can be utilized as a catalyst for oxidation reactions, in particular for the selective oxidation with molecular oxygen under mild conditions.

<span class="mw-page-title-main">DMTMM</span> Chemical compound

DMTMM is an organic triazine derivative commonly used for activation of carboxylic acids, particularly for amide synthesis. Amide coupling is one of the most common reactions in organic chemistry and DMTMM is one reagent used for that reaction. The mechanism of DMTMM coupling is similar to other common amide coupling reactions involving activated carboxylic acids. Its precursor, 2-chloro-4,6,-dimethoxy-1,3,5-triazine (CDMT), has also been used for amide coupling. DMTMM has also been used to synthesize other carboxylic functional groups such as esters and anhydrides. DMTMM is usually used in the chloride form but the tetrafluoroborate salt is also commercially available.

References

  1. Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. p. 3.316. ISBN   9781498754293.
  2. Knight, David W. (2001). "N-Hydroxysuccinimide". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rh069. ISBN   0471936235.
  3. Anderson, G.W.; Zimmerman, J. F.; Callahan, F. M. (1963). "N-Hydroxysuccinimide Esters in Peptide Synthesis". J. Am. Chem. Soc. 85 (19): 3039. doi:10.1021/ja00902a047.
  4. Camargo, Jéssica Rocha; Baccarin, Marina; Raymundo-Pereira, Paulo A.; Campos, Anderson M.; Oliveira, Geiser G.; Fatibello-Filho, Orlando; Oliveira, Osvaldo N.; Janegitz, Bruno C. (2018-11-30). "Electrochemical biosensor made with tyrosinase immobilized in a matrix of nanodiamonds and potato starch for detecting phenolic compounds". Analytica Chimica Acta. 1034: 137–143. doi:10.1016/j.aca.2018.06.001. PMID   30193627. S2CID   52174400.