Hexane-2,5-dione

Hexane-2,5-dione, C6H10O2, is a diketone and a toxic metabolite of hexane.

Symptoms
The initial symptoms of chronic hexane toxicity, attributable to hexane-2,5-dione, are tingling and cramps in the arms and legs, followed by general muscular weakness. In severe cases, atrophy of the skeletal muscles is observed, along with a loss of coordination and problems of vision.

Similar symptoms are observed in animal models. They are associated with a degeneration of the peripheral nervous system (and eventually the central nervous system), starting with the distal portions of the longer and wider nerve axons.

Mechanism of action
Hexane-2,5-dione reacts with the amine functional group; for example the amine group of the side chain of lysine residues in proteins, causing cross-linking and a loss of protein function.

The lone pair on the nitrogen attacks either of the electron deficient carbonyl carbons, losing hydrogen and protonating the oxygen. The Nitrogen is now attached to the 2 position of the chain; its lone pair again attacks the carbon of the other carbonyl. Again joining the chain, protonating the oxygen and deprotonating the nitrogen. Two water molecules are then lost from the system, creating aromaticity: 2,5-dimethlypyrrole.

Related metabolytes
Hexane-2,5-dione can be metabolically dehydrated to 2,5-dimethylfuran.

Acetonilacetons