5-Nonanone, or dibutyl ketone, is the

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 ...

with the formula (CH₃CH₂CH₂CH₂)₂CO. This colorless liquid is a symmetrical

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

Synthesis

5-Nonanone, which is potentially of interest as a diesel fuel, can be produced from

levulinic acid Levulinic acid, or 4-oxopentanoic acid, is an organic compound with the formula CH3C(O)CH2CH2CO2H. It is classified as a keto acid. This white crystalline solid is soluble in water and polar organic solvents. It is derived from degradation of cell ...

, which can be produced from fructose. Levulinic acid is converted to

valeric acid Valeric acid or pentanoic acid is a straight-chain alkyl carboxylic acid with the chemical formula . Like other low-molecular-weight carboxylic acids, it has an unpleasant odor. It is found in the perennial flowering plant ''Valeriana officina ...

, which undergoes

ketonization In organic chemistry, ketonic decarboxylation (also known as decarboxylative ketonization) is a type of organic reaction and a decarboxylation converting two equivalents of a carboxylic acid () to a symmetric ketone () by the application of heat w ...

Toxicology

Metabolic pathway

5-Nonanone was expected to be

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

to a γ-diketone (a diketone with the second oxygen three carbons away from the first, e.g. 2,5- or 3,6-diketones). Metabolic studies confirmed the ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' ω-oxidation of 5-nonanone to 2,5-nonanedione and 2-hexanone. Subsequent

oxidative Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

and decarboxylative steps also produce 2,5-hexanedione. Besides these metabolites, 38% of the 5-nonanone dose is converted to

carbon dioxide Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...

. No unchanged 5-nonanone is detected in the urine after administration. Of these metabolites, 2,5-hexanedione is believed to be the most

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

compound. Of all the aforementioned metabolites, the toxicity is believed to be due to the metabolic transformation to this γ-diketone.

Toxicological effects

In rats, the

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

of 5-nonanone is enhanced by

methyl ethyl ketone Butanone, also known as methyl ethyl ketone (MEK), is an organic compound with the formula CH3C(O)CH2CH3. This colourless liquid ketone has a sharp, sweet odor reminiscent of acetone. It is produced industrially on a large scale, but occurs in nat ...

. This suggests

induction Induction, Inducible or Inductive may refer to: Biology and medicine * Labor induction (birth/pregnancy) * Induction chemotherapy, in medicine * Induced stem cells, stem cells derived from somatic, reproductive, pluripotent or other cell t ...

microsomal In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, liv ...

oxidizing

enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

, which results in greater production of toxic metabolites. Chronic exposure to the compound has been shown to produce a clinical neuropathy, characterized by giant

axonal An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

swellings filled with

neurofilaments Neurofilaments (NF) are classed as type IV intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring 10 nm in diameter and many micrometers in length. Together with microtubules (~25 nm) and mi ...

. It also resulted in an orange/brown discoloration of the hair of the rats. Another study was done on rats to explore the enhancement of the toxicity of 5-nonanone by 5-methyl-2-octanone. The combination of these two compounds increases the neurotoxic effect of 5-nonanone approximately sixfold. When only exposed to 5-methyl-2-octanone

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

swelling was observed, indicating that metabolic activation of hepatic oxidative

may be the cause of the increase in toxicity in co-administration.

References

{{DEFAULTSORT:Nonanone, 5- Nonanones

Synthesis

Toxicology

Metabolic pathway

Toxicological effects

See also

References