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Revision as of 14:28, 23 February 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL.← Previous edit		Latest revision as of 12:31, 14 August 2024 edit undoPreimage (talk | contribs)Extended confirmed users960 edits →Chembox_Properties: Add pKb
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			{{Distinguish|Guanine|Guanosine|Guanfacine}}
	{{chembox
			{{Chembox
	| verifiedrevid = 402141819
			|Watchedfields = changed
	| Name = Guanidine
			|verifiedrevid = 443849964
	| ImageFile = Guanidine-2D-skeletal.png
			|ImageFileL1 = Guanidin.svg
	<!-- | ImageSize = 150px -->
			|ImageFileL1_Ref = {{chemboximage|correct|??}}
	| ImageName = Skeletal formula of guanidine
			|ImageNameL1 = Skeletal formula of guanidine
	| ImageFile1 = Guanidine-3D-balls.png
			|ImageFileR1 = Guanidine-2D.png
	<!-- | ImageSize1 = 150px -->
			|ImageFileR1_Ref = {{chemboximage|correct|??}}
	| ImageName1 = Ball-and-stick model of guanidine
			|ImageNameR1 = Skeletal formula of guanidine with the implicit carbon shown, and all explicit hydrogens added.
	| IUPACName = Guanidine
			|ImageFileL2 = Guanidine-3D-balls.png
	| Section1 = {{Chembox Identifiers
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		|ImageFileL2_Ref = {{chemboximage|correct|??}}
			|ImageNameL2 = Ball and stick model of guanidine
	| ChemSpiderID = 3400
			|ImageFileR2 = Guanidine-3D-vdW.png
	| PubChem = 3520
	| UNII_Ref = {{fdacite|correct|FDA}}		|ImageFileR2_Ref = {{chemboximage|correct|??}}
			|ImageNameR2 = Spacefill model of guanidine
	| UNII = JU58VJ6Y3B
			|PIN = Guanidine<ref>{{cite book |author=] |date=2014 |title=Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 |publisher=] |pages=883 |doi=10.1039/9781849733069 |isbn=978-0-85404-182-4}}</ref>
	| InChI = 1/CH5N3/c2-1(3)4/h(H5,2,3,4)
			|OtherNames = Iminomethanediamine
	| InChIKey = ZRALSGWEFCBTJO-UHFFFAOYAY
			|Section1={{Chembox Identifiers
	| ChEMBL = 821
			|IUPHAR_ligand = 4783
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			|CASNo = 113-00-8
	| StdInChI = 1S/CH5N3/c2-1(3)4/h(H5,2,3,4)
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		|CASNo_Ref = {{cascite|correct|CAS}}
			|PubChem = 3520
	| StdInChIKey = ZRALSGWEFCBTJO-UHFFFAOYSA-N
			|ChemSpiderID = 3400
	| CASNo = 113-00-8
	| CASNo_Ref = {{cascite|correct|CAS}}		|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			|UNII = JU58VJ6Y3B
	| SMILES = C(=N)(N)N
			|UNII_Ref = {{fdacite|correct|FDA}}
	}}
			|EINECS = 204-021-8
	| Section2 = {{Chembox Properties
			|DrugBank = DB00536
	| Formula = CH<sub>5</sub>N<sub>3</sub>
			|DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| MolarMass = 59.07 g/mol
			|MeSHName = Guanidine
	| Density =
			|ChEBI = 42820
	| MeltingPt = 50 °C
			|ChEBI_Ref = {{ebicite|correct|EBI}}
	| BoilingPt =
	| pKb = 1.5		|ChEMBL = 821
			|ChEMBL_Ref = {{ebicite|correct|EBI}}
	}}
			|Beilstein = 506044
	| Section7 = {{Chembox Hazards
			|Gmelin = 100679
	| ExternalMSDS =
			|SMILES = NC(N)=N
	| EUIndex = Not listed
			|StdInChI = 1S/CH5N3/c2-1(3)4/h(H5,2,3,4)
	| MainHazards =
			|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| NFPA-H =
			|StdInChIKey = ZRALSGWEFCBTJO-UHFFFAOYSA-N
	| NFPA-F =
			|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| NFPA-R =
	| FlashPt =
	| RPhrases =
	| SPhrases =
	}}
	| Section8 = {{Chembox Related
	| OtherFunctn =
	| Function =
	| OtherCpds = ]<br/>]
	}}
	}}		}}
			|Section2={{Chembox Properties
			|C=1 | H=5 | N=3
			|MeltingPtC = 50
			|pKb = 0.4<ref name=Perrin/>
			|ConjugateAcid = Guanidinium
			|LogP = −1.251
			}}
			|Section3={{Chembox Thermochemistry
			|DeltaHf = −57 – −55 kJ&nbsp;mol<sup>−1</sup>
			|DeltaHc = −1.0511 – −1.0531 MJ&nbsp;mol<sup>−1</sup>
			}}
			|Section4={{Chembox Pharmacology
			|HalfLife = 7–8 hours
			}}
			|Section5={{Chembox Hazards
			|LD50 = 475 mg/kg (oral, rat)<ref>{{cite web|url=https://chem.nlm.nih.gov/chemidplus/rn/50-01-1|website=ChemIDplus|publisher=]|title=Guanidine hydrochloride|access-date=2014-08-10|archive-date=2014-08-12|archive-url=https://web.archive.org/web/20140812205443/https://chem.nlm.nih.gov/chemidplus/rn/50-01-1|url-status=live}}</ref>
			}}
			|Section6={{Chembox Related
			|OtherCompounds = {{Unbulleted list|]|]}}
			}}
			}}
			'''Guanidine''' is the compound with the formula HNC(NH<sub>2</sub>)<sub>2</sub>. It is a colourless solid that dissolves in ] solvents. It is a ] that is used in the production of ] and ]. It is found in ] predominantly in patients experiencing renal failure.<ref>{{cite journal | vauthors = Sawynok J, Dawborn JK | title = Plasma concentration and urinary excretion of guanidine derivatives in normal subjects and patients with renal failure | journal = Clinical and Experimental Pharmacology & Physiology | volume = 2 | issue = 1 | pages = 1–15 | year = 1975 | pmid = 1126056 | doi = 10.1111/j.1440-1681.1975.tb02368.x | s2cid = 41794868 }}</ref> A guanidine ] also appears in larger organic molecules, including on the side chain of ].
			== Structure ==
	'''Guanidine''' is a ] compound of strong ] formed by the ] of ]. It is used in the manufacture of ] and ]. It is found in ] as a normal product of protein ]. The molecule was first synthesized in 1861 by the oxidative degradation of an aromatic natural product, ], isolated from Peruvian ].<ref>A. Strecker, ''Liebigs Ann. Chem.'' '''1861''', ''118'', 151.</ref> Despite the simplicity of the molecule, the crystal structure was first described 148 years later.<ref>T. Yamada, X. Liu, U. Englert, H. Yamane, R. Dronskowski, ''Chem. Eur. J.'' '''2009''', ''15'', 5651.</ref>
			Guanidine can be thought of as a nitrogenous analogue of ]. That is, the C=O group in carbonic acid is replaced by a C=NH group, and each OH is replaced by a {{chem|NH|2}} group.<ref>{{cite journal | vauthors = Göbel M, Klapötke TM | title = First structural characterization of guanidine, HN=C(NH(2))(2) | journal = Chemical Communications | volume = 43 | issue = 30 | pages = 3180–3182 | date = August 2007 | pmid = 17653381 | doi = 10.1039/B705100J }}</ref> ] can be seen as the carbon analogue in much the same way. A detailed crystallographic analysis of guanidine was elucidated 148 years after its first synthesis, despite the simplicity of the molecule.<ref>{{cite journal | vauthors = Yamada T, Liu X, Englert U, Yamane H, Dronskowski R | title = Solid-state structure of free base guanidine achieved at last | journal = Chemistry: A European Journal | volume = 15 | issue = 23 | pages = 5651–5655 | date = June 2009 | pmid = 19388036 | doi = 10.1002/chem.200900508 }}</ref> In 2013, the positions of the hydrogen atoms and their displacement parameters were accurately determined using single-crystal neutron diffraction.<ref>{{cite journal | vauthors = Sawinski PK, Meven M, Englert U, Dronskowski R | journal = Crystal Growth & Design | year = 2013 | volume = 13 |issue=4 | pages = 1730–5 | doi = 10.1021/cg400054k | title = Single-Crystal Neutron Diffraction Study on Guanidine, CN<sub>3</sub>H<sub>5</sub> |doi-access=free }}</ref>
	]
			==Production==
	==Guanidinium cation==
			Guanidine can be obtained from natural sources, being first isolated in 1861 by ] via the oxidative degradation of an aromatic natural product, ], isolated from Peruvian ].<ref name=Ullmann/><ref>{{cite journal | vauthors = Strecker A | author-link = Adolph Strecker | journal = Liebigs Ann. Chem. | year = 1861 | volume = 118 | pages = 151–177 | issue = 2 | title = Untersuchungen über die chemischen Beziehungen zwischen Guanin, Xanthin, Theobromin, Caffeïn und Kreatinin | trans-title = Studies on the chemical relationships between guanine, xanthine, theobromine, caffeine and creatinine | doi = 10.1002/jlac.18611180203 | url = https://zenodo.org/record/1427163 | access-date = 2019-07-02 | archive-date = 2021-07-16 | archive-url = https://web.archive.org/web/20210716154230/https://zenodo.org/record/1427163 | url-status = live }}</ref>
	Guanidine is protonated in physiological conditions. This ] is called the '''guanidinium''' ], <sup>+</sup>. The guanidinium cation has a charge of ] and a ] of 12.5.
			A laboratory method of producing guanidine is gentle (180-190&nbsp;°C) thermal decomposition of dry ] in anhydrous conditions:
			:{{chem2|3 NH4SCN -> 2 CH5N3 + H2S + CS2}}
			The commercial route involves a two step process starting with the reaction of ] with ] salts. Via the intermediacy of ], this ] step affords salts of the guanidinium cation (see below). In the second step, the salt is treated with base, such as ].<ref name=Ullmann>{{Ullmann| vauthors = Güthner T, Mertschenk B, Schulz B |title=Guanidine and Derivatives |doi=10.1002/14356007.a12_545.pub2}}</ref>
			]s (S-alkylated ]s) react with ]s to give ] salts:<ref>{{cite journal|last1=Palmer|first1=David C.|title=''S''-Methylisothiourea|journal=E-EROS Encyclopedia of Reagents for Organic Synthesis|year=2001|doi=10.1002/047084289X.rm199s|isbn=0471936235}}</ref>
			:RNH<sub>2</sub> + <sup>+</sup>X<sup>−</sup> → <sup>+</sup>X<sup>−</sup> + CH<sub>3</sub>SH
			The resulting guanidinium ions can often be deprotonated to give the guanidine. This approach is sometimes called the Rathke synthesis, in honor of its discoverer. after ]<ref>{{cite journal|title=Heinrich Bernhard Rathke. (1840-1923)|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|date=8 October 1924|volume=57|issue=9|pages=A83–A92|doi=10.1002/cber.19240570929|doi-access=free}}</ref><ref>{{cite journal|last1=Rathke|first1=B.|title=Ueber Derivate und Constitution des Schwefelharnstoffs|journal=Berichte der Deutschen Chemischen Gesellschaft|date=July 1881|volume=14|issue=2|pages=1774–1780|doi=10.1002/cber.18810140247|url=https://zenodo.org/record/1425246}}</ref>
			==Chemistry==
			===Guanidinium cation===
			The ] is called the '''guanidinium''' ], ({{chem|C(NH|2|)|3|+}}). This planar, symmetric ion consists of three ] groups each bonded to the central carbon atom with a covalent bond of ] 4/3. It is a highly stable ] cation in aqueous solution due to the efficient ] of the charge and efficient ] by water molecules. As a result, its ] is 13.6<ref name=Perrin>{{cite book| vauthors = Perrin DD |title=Dissociation Constants of Organic Bases in Aqueous Solution |publisher=Butterworths |location=London |date=1972 |edition=Supplement }}</ref> (p''K''<sub>b</sub> of 0.4) meaning that guanidine is a very strong base in water; in neutral water, it exists almost exclusively as guanidinium. Due to this, most guanidine derivatives are salts containing the conjugate acid.
	<gallery>		<gallery>
	Image:Guanidinium-ion-3D-balls.png|<center>]</center>		Image:Guanidinium-ion-3D-balls.png|{{center|]}}
	Image:Guanidinium-ion-2D-skeletal.png|<center>]</center>		Image:Guanidinium-ion-2D-skeletal.png|{{center|]}}
	Image:Guanidinium-ion-canonical-forms-2D-skeletal.png|<center>canonical forms</center>		Image:Guanidinium-ion-canonical-forms-2D-skeletal.png|{{center|canonical forms}}
	</gallery>		</gallery>
			===Testing for guanidine===
	Notable guanidinium salts include ] (GndCl), which has ] properties and is used to denature proteins. Empirically, guanidine hydrochloride is known to denature proteins with a linear relationship between concentration and ] of unfolding. Another such salt is ].
			Guanidine can be selectively detected using sodium 1,2-naphthoquinone-4-sulfonic acid (]) and acidified urea.<ref>{{Cite journal | vauthors = Sullivan MX |date=1935-10-01 |title=A Colorimetric Test for Guanidine |journal=Proceedings of the Society for Experimental Biology and Medicine |language=en |volume=33 |issue=1 |pages=106–108 |doi=10.3181/00379727-33-8270C |s2cid=88290359 |issn=0037-9727}}</ref>
			==Uses==
			===Industry===
			The main salt of commercial interest is ] {{chem|NO|3}}. It is used as a propellant, for example in ]s.
			===Medicine===
			Since the Middle Ages in Europe, guanidine has been used to treat diabetes as the active ] ingredient in ]. Due to its long-term ], further research for blood sugar control was suspended at first after the discovery of insulin. Later development of nontoxic, safe ] led to the long-used first-line diabetes control medicine ], introduced to Europe in the 1950s & United States in 1995 and now prescribed to over 17 million patients per year in the US.<ref name="Treatment approach to type 2 diabet">{{cite journal | vauthors = Blaslov K, Naranđa FS, Kruljac I, Renar IP | title = Treatment approach to type 2 diabetes: Past, present and future | journal = World Journal of Diabetes | volume = 9 | issue = 12 | pages = 209–219 | date = December 2018 | pmid = 30588282 | pmc = 6304295 | doi = 10.4239/wjd.v9.i12.209 | doi-access = free }}</ref><ref>{{Cite web|title=The Top 300 of 2019|url=https://clincalc.com/DrugStats/Top300Drugs.aspx|access-date=2022-02-17|website=clincalc.com|archive-date=2021-02-12|archive-url=https://web.archive.org/web/20210212142534/https://clincalc.com/DrugStats/Top300Drugs.aspx|url-status=live}}</ref>
			Guanidinium chloride<ref name="Treatment approach to type 2 diabet"/> is a now-controversial ] in treatment of ]. Recent studies have shown some significant subsets of patients who see no improvement after the administration of this drug.<ref>{{cite book| vauthors = Brook I |title=Pediatric Anaerobic Infections: Diagnosis and Management|publisher=Taylor & Francis|year=2001|isbn=0824741862|edition=3rd|page=529}}<!-- Please confirm page correct for edition--></ref>
			===Biochemistry===
			Guanidine exists protonated, as guanidinium, in solution at physiological pH.
			] (also known as guanidine hydrochloride) has ] properties and is used to denature proteins. Guanidinium chloride is known to denature proteins with a linear relationship between concentration and ] of unfolding. In aqueous solutions containing 6&nbsp;] guanidinium chloride, almost all ] lose their entire ] and become ] peptide chains. ] is also used for its denaturing effect on various biological samples.
			Recent studies suggest that guanidinium is produced by bacteria as a toxic byproduct. To alleviate the toxicity of guanidinium, bacteria have developed a class of transporters known as guanidinium exporters or Gdx proteins to expel the extra amounts of this ion to the outside of the cell.<ref>{{cite journal | vauthors = Kermani AA, Macdonald CB, Gundepudi R, Stockbridge RB | title = Guanidinium export is the primal function of SMR family transporters | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 12 | pages = 3060–3065 | date = March 2018 | pmid = 29507227 | pmc = 5866581 | doi = 10.1073/pnas.1719187115 | bibcode = 2018PNAS..115.3060K | doi-access = free }}</ref> Gdx proteins, are highly selective for guanidinium and mono-substituted guanidinyl compounds and share an overlapping set of non-canonical substrates with drug exporter EmrE.<ref>{{cite journal | vauthors = Kermani AA, Macdonald CB, Burata OE, Ben Koff B, Koide A, Denbaum E, Koide S, Stockbridge RB | display-authors = 6 | title = The structural basis of promiscuity in small multidrug resistance transporters | journal = Nature Communications | volume = 11 | issue = 1 | pages = 6064 | date = November 2020 | pmid = 33247110 | doi = 10.1038/s41467-020-19820-8 | pmc = 7695847 | bibcode = 2020NatCo..11.6064K }}</ref>
			===Other===
			Guanidinium hydroxide is the active ingredient in some non-lye ]s.
	==Guanidine derivatives==		==Guanidine derivatives==
	]		]
	'''Guanidines''' are a group of ]s sharing a common ] with the general structure (R<sup>1</sup>R<sup>2</sup>N)(R<sup>3</sup>R<sup>4</sup>N)C=N-R<sup>5</sup>. The central bond within this group is that of an ], and the group is related structurally to amidines and ureas. Examples of guanidines are ], ] and ]. Another derivative is guanidinium hydroxide, the active ingredient in some non-lye hair relaxers.		'''Guanidines''' are a group of ]s sharing a common ] with the general structure {{chem|(R|1|R|2|N)(R|3|R|4|N)C{{=}}N−R|5}}. The central bond within this group is that of an ], and the group is related structurally to amidines and ureas. Examples of guanidines are ], ], ], and ].
	'''Guanidinium salts''' are well known for their denaturing action on proteins; ] is one of the most effective ]. In 6 M aqueous GndHCl almost all ] lose their ordered "secondary structure" (that results from intramolecular noncovalent interactions) and become "randomly coiled"; that is, their secondary structure interactions are disrupted by the dissolved guanidinium, leaving only the primary covalent structure of their polyamide backbones.
			] is an ] guanidine.<ref name=Witters2001>{{cite journal | vauthors = Witters LA | title = The blooming of the French lilac | journal = The Journal of Clinical Investigation | volume = 108 | issue = 8 | pages = 1105–1107 | date = October 2001 | pmid = 11602616 | pmc = 209536 | doi = 10.1172/JCI14178 }}</ref>
			{{Clear|left}}
			== See also ==
			*]
			*]
			*]
	==See also==		== References==
	*]
	*]
			{{Reflist}}
	==References==
	<references/>
			{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}
	{{Antihypertensives and diuretics}}		{{Antihypertensives and diuretics}}
			{{Authority control}}
	]
	]		]
			]
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	]