Guanidinium chloride or guanidine hydrochloride, usually abbreviated GdmCl and sometimes GdnHCl or GuHCl, is the

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative n ...

salt of

guanidine Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...

Structure

Guanidinium chloride crystallizes in orthorhombic

space group In mathematics, physics and chemistry, a space group is the symmetry group of an object in space, usually in three dimensions. The elements of a space group (its symmetry operations) are the rigid transformations of an object that leave it unchan ...

''Pbca''. The

crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystal, crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric pat ...

consists of a network of

guanidinium Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...

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 ...

s and

chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...

anions 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 conven ...

linked by N–H···Cl

hydrogen bond In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...

Acidity

Guanidinium chloride is a weak acid with a pK_a of 13.6. The reason that it is such a weak acid is the complete delocalisation of the positive charge through 3 nitrogen atoms (plus a little bit positive charge on carbon). However, some stronger bases can deprotonate it, such as

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and alkali ...

: C(NH2)3+ + OH- <=>> HNC(NH2)2 + H2O The equilibrium is not complete because the acidity difference between guanidinium and water is not large (The approximate pK_a values: 13.6 vs 15.7). Complete

deprotonation Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.ed ...

should be done with extremely strong bases, such as

lithium diisopropylamide Lithium diisopropylamide (commonly abbreviated LDA) is a chemical compound with the molecular formula . It is used as a strong base and has been widely utilized due to its good solubility in non-polar organic solvents and non-nucleophilic nature ...

. C(NH2)3+Cl- + Li+N(C3H7)2- -> HNC(NH2)2 + HN(C3H7)2 + LiCl

Use in protein denaturation

Guanidinium chloride is a strong chaotrope and one of the strongest denaturants used in physiochemical studies of

protein folding Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...

. It also has the ability to decrease enzyme activity and increase the solubility of hydrophobic molecules. At high concentrations of guanidinium chloride (e.g., 6 M),

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 lose their ordered

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

, and they tend to become randomly coiled, i.e. they do not contain any residual structure. However, at concentrations in the millimolar range in vivo, guanidinium chloride has been shown to "cure"

prion Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...

positive yeast cells (i.e. cells exhibiting a prion positive phenotype revert to a prion negative phenotype). This is the result of inhibition of the

Hsp104 Hsp104 is a heat-shock protein. It is known to reverse toxicity of mutant α-synuclein, TDP-43, FUS, and TAF15 in yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast origin ...

chaperone protein known to play an important role in prion fiber fragmentation and propagation.

Historical survey

Petrunkin and Petrunkin (1927, 1928) appear to be the first who studied the binding of GnHCl to

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 ...

and a mixture of thermally denatured protein from brain extract. Greenstein (1938, 1939), however, appears to be the first to discover the high denaturing action of guanidinium

halide In chemistry, a halide (rarely halogenide) is a binary chemical compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative (or more electropositive) than the halogen, to make a fluor ...

s and thiocyanates in following the liberation of sulfhydryl groups in

ovalbumin Ovalbumin (abbreviated OVA) is the main protein found in egg white, making up approximately 55% of the total protein. Ovalbumin displays sequence and three-dimensional homology to the serpin superfamily, but unlike most serpins it is not a serin ...

and few other proteins as a function of salt concentration.

Medical uses

Guanidine hydrochloride is indicated for the reduction of the symptoms of muscle weakness and easy fatigability associated with Eaton-Lambert syndrome. It is not indicated for treating myasthenia gravis. It apparently acts by enhancing the release of acetylcholine following a nerve impulse. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes. Initial dosage is usually between 10 and 15 mg/kg (5 to 7 mg/pound) of body weight per day in 3 or 4 divided doses. This dosage may be gradually increased to a total daily dosage of 35 mg/kg (16 mg/pound) of body weight per day or up to the development of side effects. Side effects include increased peristalsis and diarrhea. Fatal bone-marrow suppression, apparently dose related, can occur with guanidine.

References

{{Reflist Guanidinium compounds Protein structure Chaotropic agents Chlorides