Guanidine is the compound with the formula HNC(NH₂)₂. It is a colourless solid that dissolves in

polar Polar may refer to: Geography Polar may refer to: * Geographical pole, either of two fixed points on the surface of a rotating body or planet, at 90 degrees from the equator, based on the axis around which a body rotates * Polar climate, the c ...

solvents. It is a strong base that is used in the production of

plastics Plastics are a wide range of synthetic polymers, synthetic or semi-synthetic materials that use polymers as a main ingredient. Their Plasticity (physics), plasticity makes it possible for plastics to be Injection moulding, moulded, Extrusion, e ...

and

explosives An explosive (or explosive material) is a reactive substance that contains a great amount of potential energy that can produce an explosion if released suddenly, usually accompanied by the production of light, heat, sound, and pressure. An expl ...

. It is found in

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

predominantly in patients experiencing renal failure. A guanidine

moiety Moiety may refer to: Chemistry * Moiety (chemistry), a part or functional group of a molecule ** Moiety conservation, conservation of a subgroup in a chemical species Anthropology * Moiety (kinship), either of two groups into which a society is ...

also appears in larger organic molecules, including on the side chain of

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

Structure

Guanidine can be thought of as a nitrogenous analogue of carbonic acid. That is, the C=O group in carbonic acid is replaced by a C=NH group, and each OH is replaced by a group.

Isobutene Isobutylene (or 2-methylpropene) is a hydrocarbon with the chemical formula . It is a four-carbon branched alkene (olefin), one of the four isomers of butylene. It is a colorless flammable gas, and is of considerable industrial value. Productio ...

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. In 2013, the positions of the hydrogen atoms and their displacement parameters were accurately determined using single-crystal neutron diffraction.

Production

Guanidine can be obtained from natural sources, being first isolated by

Adolph Strecker Adolph Strecker (October 21, 1822 – November 7, 1871) was a German chemist who is remembered primarily for his work with amino acids. Life and work Strecker was born in Darmstadt, the son of Friedrich Ludwig Strecker, an archivist working for ...

via the degradation of

guanine Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called ...

. It was first synthesized in 1861 by the oxidative degradation of an aromatic natural product,

, isolated from Peruvian

guano Guano (Spanish from qu, wanu) is the accumulated excrement of seabirds or bats. As a manure, guano is a highly effective fertilizer due to the high content of nitrogen, phosphate, and potassium, all key nutrients essential for plant growth. G ...

. A laboratory method of producing guanidine is gentle (180-190 °C) thermal decomposition of dry

ammonium thiocyanate Ammonium thiocyanate is an inorganic compound with the formula NH4SCN. It is the salt of the ammonium cation and the thiocyanate anion. Uses Ammonium thiocyanate is used in the manufacture of herbicides, thiourea, and transparent artificial resin ...

in anhydrous conditions: :3 NH4SCN -> 2 CH5N3 + H2S + CS2 The commercial route involves a two step process starting with the reaction of

dicyandiamide 2-Cyanoguanidine is a nitrile derived from guanidine. It is a dimer of cyanamide, from which it can be prepared. 2-Cyanoguanidine is a colourless solid that is soluble in water, acetone, and alcohol, but not nonpolar organic solvents. Production ...

with

ammonium The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary a ...

salts. Via the intermediacy of

biguanidine Biguanide () is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea. Synthesis Biguanide can be obtained from ...

, this

ammonolysis In chemistry, ammonolysis (/am·mo·nol·y·sis/) is the process of splitting ammonia into NH2- + H+. Ammonolysis reactions can be conducted with organic compounds to produce amines (molecules containing a nitrogen atom with a lone pair, :N), o ...

step affords salts of the guanidinium cation (see below). In the second step, the salt is treated with base, such as

sodium methoxide Sodium methoxide is the simplest sodium alkoxide. With the formula , it is a white solid, which is formed by the deprotonation of methanol. Itis a widely used reagent in industry and the laboratory. It is also a dangerously caustic base. P ...

Chemistry

Guanidinium cation

With a p''K''_b of 0.4, guanidine is a strong base. Most guanidine derivatives are in fact salts containing the conjugate acid. The

conjugate acid A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid donates a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a ...

is called the guanidinium

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

, (). This planar, symmetric ion consists of three

amino In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...

groups each bonded to the central carbon atom with a covalent bond of order 4/3. It is a highly stable +1 cation in aqueous solution due to the efficient

resonance stabilization In chemistry, resonance, also called mesomerism, is a way of describing bonding in certain molecules or polyatomic ions by the combination of several contributing structures (or ''forms'', also variously known as ''resonance structures'' or '' ...

of the charge and efficient

solvation Solvation (or dissolution) describes the interaction of a solvent with dissolved molecules. Both ionized and uncharged molecules interact strongly with a solvent, and the strength and nature of this interaction influence many properties of the ...

by water molecules. As a result, its p''K''_aH is 13.6 meaning that guanidine is a very strong base in water; in neutral water, it exists almost exclusively as guanidinium. Image:Guanidinium-ion-3D-balls.png, Image:Guanidinium-ion-2D-skeletal.png, Image:Guanidinium-ion-canonical-forms-2D-skeletal.png,

Testing for guanidine

Guanidine can be selectively detected using sodium 1,2-naphthoquinone-4-sulfonic acid (

Folin's reagent Folin's reagent or sodium 1,2-naphthoquinone-4-sulfonate is a chemical reagent used as a derivatizing agent to measure levels of amines and amino acids. The reagent reacts with them in alkaline solution to produce a fluorescent material that can ...

) and acidified urea.

Uses

Industry

The main salt of commercial interest is the nitrate ()₃ It is used as a propellant, for example in

air bag An airbag is a vehicle occupant-restraint system using a bag designed to inflate extremely quickly, then quickly deflate during a Traffic collision, collision. It consists of the airbag cushion, a flexible fabric bag, an inflation module, and a ...

Medicine

Since the Middle Ages in Europe, guanidine has been used to treat diabetes as the active

antihyperglycemic Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists (liraglutide, exenatide, and others), and pramlintide, all are administered orally and are th ...

ingredient in French lilac. Due to its long-term

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...

, further research for blood sugar control was suspended at first after the discovery of insulin. Later development of nontoxic, safe

biguanides Biguanide () is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea. Synthesis Biguanide can be obtained from ...

led to the long-used first-line diabetes control medicine

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...

, introduced to Europe in the 1950s & United States in 1995 and now prescribed to over 17 million patients per year in the US. Guanidinium chloride is a now-controversial adjuant in treatment of

botulism Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium ''Clostridium botulinum''. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakne ...

. Recent studies have shown some significant subsets of patients who see no improvement after the administration of this drug.

Biochemistry

Guanidine exists protonated, as guanidinium, in solution at physiological pH.

Guanidinium chloride Guanidinium chloride or guanidine hydrochloride, usually abbreviated GdmCl and sometimes GdnHCl or GuHCl, is the hydrochloride salt of guanidine. Structure Guanidinium chloride crystallizes in orthorhombic space group ''Pbca''. The crystal stru ...

(also known as guanidine hydrochloride) has

chaotropic Chaotropicity describes the entropic disordering of lipid bilayers and other biomacromolecules which is caused by substances dissolved in water. According to the original usage and work carried out on cellular stress mechanisms and responses, ch ...

properties and is used to denature proteins. Guanidinium chloride is known to denature proteins with a linear relationship between concentration and free energy of unfolding. In aqueous solutions containing 6 M guanidinium chloride, almost all

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 ...

lose their entire

secondary structure Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...

and become randomly coiled peptide chains.

Guanidinium thiocyanate Guanidinium thiocyanate (GTC) or guanidinium isothiocyanate (GITC) is a chemical compound used as a general protein denaturant, being a chaotropic agent, although it is most commonly used as a nucleic acid protector in the extraction of DNA and ...

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. 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.

Other

Guanidinium hydroxide is the active ingredient in some non-lye

hair relaxer A relaxer is a type of lotion or cream generally used by people with tight curls or very curly hair which makes hair easier to straighten by chemically "relaxing" the natural curls. The active agent is usually a strong alkali, although some formu ...

Guanidine derivatives

Guanidines are a group of

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

s sharing a common

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...

with the general structure . The central bond within this group is that of an

imine In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bo ...

, and the group is related structurally to amidines and ureas. Examples of guanidines are

triazabicyclodecene Triazabicyclodecene (1,5,7-triazabicyclo .4.0ec-5-ene or TBD) is an organic compound consisting of a bicyclic guanidine. For a charge-neutral compound, it is a relatively strong base that is effectively for a variety of organic transformations. ...

saxitoxin Saxitoxin (STX) is a potent neurotoxin and the best-known paralytic shellfish toxin (PST). Ingestion of saxitoxin by humans, usually by consumption of shellfish contaminated by toxic algal blooms, is responsible for the illness known as paralyt ...

, and

creatine Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. It exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate ( ...

Galegine Galegine is a toxic chemical compound that has been isolated from Goat's rue (''Galega officinalis''). It has also been found to be the principal cause of the toxicity of poison sedge (''Schoenus asperocarpus''). Galegine was used in the 1920s ...

is an

isoamylene 2-Methyl-2-butene, 2m2b, 2-methylbut-2-ene, also beta-isoamylene is an alkene hydrocarbon with the molecular formula C5H10. Used as a free radical scavenger in Chloroform, trichloromethane (chloroform) and dichloromethane (methylene chloride). J ...

guanidine.

References

{{Authority control Guanidines Bases (chemistry)