Hemithioacetal, also known as hemimercaptal, is an organic functional group

Functional group

In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...

 with the general formula RCH(OR)SR. They form in a spontaneous reaction between a thiol

Thiol

In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

 and an aldehyde

Aldehyde

An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....

. Since the formerly carbonyl carbon bears four different substituents, hemiacetals are chiral. Hemithioacetals are usually intermediates in the catalytic reactions and usually arise via acid or base catalysis

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

. The hemithioacetal features vicinal

Vicinal

Vicinal may refer to:* Vicinal , stands for any two functional groups bonded to two adjacent atoms.* Vicinal , a word where all letters have alphabetic neighbors....

 hydroxyl

Hydroxyl

A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...

 and thioether

Thioether

A thioether is a functional group in organosulfur chemistry with the connectivity C-S-C as shown on right. Like many other sulfur-containing compounds, volatile thioethers have foul odors. A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen...

 functionalities. Hemithioacetals are usually unstable, degrading into thiol and aldehyde.

RCHO + R’SH RCH(OH)(SR’)

Hemithioacetals in nature

Glyoxalase I, which is part of the glyoxalase system present in the cytosol

Cytosol

The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

, catalyzes the conversion of α-oxoaldehyde (RCOCHO) and the thiol glutathione

Glutathione

Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

 (GSH) to S-2-hydroxyacylglutathione derivatives [RCH(OH)CO-SG]. The catalytic mechanism involves an intermediate hemithioacetal adduct [RCOCH(OH)-SG]. The spontaneous reaction forms methylglyoxal

Methylglyoxal

Methylglyoxal, also called pyruvaldehyde or 2-oxopropanal is the aldehyde form of pyruvic acid. It has two carbonyl groups, so it is a dicarbonyl compound. Methylglyoxal is both an aldehyde and a ketone....

-glutathione hemithioacetal and human glyoxalse I.

A hemithioacetal is invoked in the mechanism of prenylcysteine lyase

Lyase

In biochemistry, a lyase is an enzyme that catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure...

. In catalytic mechanism, S-farnesylcysteine is oxidized by flavin

Flavin

Flavin is the common name for a group of organic compounds based on pteridine, formed by the tricyclic heteronuclear organic ring isoalloxazine. The biochemical source is the vitamin riboflavin...

 to a thiocarbenium ion. The thiocarbenium ion ([(RS)C(R’)(H)]⁺) hydrolyzes to form the hemithioacetal. After formation, the hemithioacetal breaks into hydrogen peroxide

Hydrogen peroxide

Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

, farnesal, and cysteine

Cysteine

Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

.

Isolable hemithioacetal

Hemithioacetals are ordinarily unstable because they readily dissociate into thiol and aldehyde. However, some isolable hemithioacetals have been reported. The few isolable hemithioacetals are all cyclic. The cyclic structure of the hemithioacetal disfavors dissociation. One example of the cyclic hemithioacetal is O-1-naphthylurethane. With 1-naphthyl isocyanate in the presence of triethylamine

Triethylamine

Triethylamine is the chemical compound with the formula N3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine, for which TEA is also a common abbreviation....

, tetrahydro-2-hydroxythiophen forms O-1-naphthylurethane, which retains cyclic form. Another isolable hemithioacetal can be prepared by addition of thiol to methyl glyoxalate. The stability of hemithioacetal is enhanced in the presence of acid, since any racemisation process (dissociation) is slowed. The other approach to isolable hemithioacetals uses carbonyl groups that form stable hydrates. For example, a thiol (R’SH) reacts with hexafluoroacetone trihydrate. A stable hemithioacetal, which can be isolated, is obtained.