carbamate

Chemical structure of carbamates

Carbamates, or urethanes, are a group of organic compounds sharing a common functional group with the general structure R¹-O-(CO)NR²-R³. Carbamates are esters of carbamic acid, NH₂COOH, an unstable compound with R¹ = R² = R³ = H. Carbamic acid is an unstable compound because of the lability of the H-groups, leading upon exposure to water to rearrangements that lead to the decomposition to ammonium bicarbonate. Since carbamic acid contains a nitrogen attached to a carbonyl group, it is also an amide. Therefore, carbamate esters may have alkyl or aryl groups substituted on the nitrogen, or the amide function. For example, ethyl carbamate (trivial name "urethane"), is unsubstituted, whereas ethyl N–methylcarbamate has a methyl group attached to the nitrogen (see methyl isocyanate for formation of N-methylcarbamates).

Carbamates in biochemistry

A nitrogen-substituted carbamic acid is formed when a carbon dioxide molecule reacts with the amino terminus of a peptide chain or an amino group of an amino acid, adding a COO⁻ group to it and releasing a cation (H⁺ ion) to form a carbamate ion.

"R" stands for the atoms attached to the other end of the nitrogen atom of the amino group. Note that the COO⁻ group is a resonance structure, so the single bonds both show a degree of double-bond character, and the charge is delocalised over the two oxygen atoms. This reaction is reversible (with equilibrium constant K << 1 in the above reaction), as the N–C bond is highly labile.

Some occurrences of carbamate groups in nature

In hemoglobin, carbamate groups are formed when carbon dioxide molecules bond with the amino termini of the globin chains. This helps to stabilize the protein when it becomes deoxyhemoglobin and increases the likelihood of the release of remaining oxygen molecules bound to the protein.

Ribulose 1,5-bisphosphate carboxylase/oxygenase (the enzyme required to fix a carbon dioxide molecule at the start of the Calvin cycle) also requires the formation of a carbamate to function. At the active site of the enzyme, a Mg²⁺ ion is bound to a glutamate residue, an aspartate residue and a lysine carbamate, which hold the ion in place. The carbamate is formed when an uncharged lysine side-chain near the ion reacts with a carbon dioxide molecule from the air (not the substrate carbon dioxide molecule), which then renders it charged, and, therefore, able to bind the Mg²⁺ ion.

Commercial carbamate compounds

A group of insecticides also contains the carbamate functional group, including aldicarb, carbofuran, furadan, fenoxycarb, carbaryl (Sevin), ethienocarb, and fenobucarb. These insecticides can cause cholinesterase inhibition poisoning by reversibly inactivating the enzyme acetylcholinesterase. The organophosphate pesticides also inhibit this enzyme, though irreversibly, and cause a more severe form of cholinergic poisoning.

Polyurethanes contain multiple carbamate groups as part of their structure, but urethane is not a component of polyurethanes. These polymers have a wide range of properties and are commercially available as foams, elastomers, and solids.

Urethane or ethyl carbamate is occasionally used as a veterinary medicine.

In addition, some carbamates are used in human pharmacotherapy, for example, the cholinesterase inhibitors neostigmine and rivastigmine, whose chemical structure is based on the natural alkaloid physostigmine. Other examples are meprobamate and its derivatives like carisoprodol, felbamate, and tybamate, a class of anxiolytic and muscle relaxant drugs widely used in the 60s before the rise of benzodiazepines, and still used nowadays in some cases.

The insect repellent icaridin is a substituted carbamate.

See also

• Methyl carbamate
• Urethane
• Polyurethane