Nuclear magnetic resonance studies of 6-hydroxydopamine and its interactions with SH-containing model compounds. Evaluation of possible mechanism for neurocytotoxicity.
6-Hydroxydopamine (I) is a well-known neurocytotoxic agent which has become an important tool in many neurochemical studies in recent years. Biochemical investigations of the mechanism of action of 6-hydroxydopamine indicated that this amine binds covalently and irreversibly to proteins. In the present work, molecular properties of 6-hydroxydopamine in aqueous solution such as self-association, ionization, intramolecular conformations, and possible cyclization were investigated using 1H nuclear magnetic resonance spectroscopy. A model study for the interaction of 6-hydroxydopamine with proteins was undertaken by using SH-containing molecules: cysteine, glutathione, and bovine serum albumin. The binding of these compounds to 6-hydroxydopamine was found to cause labilization of the hydrogen attached to C2 of the amine aromatic ring. This effect was interpreted in  terms of nucleophilic attack of RS- on C1 of 6-hydroxydopamine. A proposed model for neurocytotoxicity is discussed.
D003545:Cysteine; D005978:Glutathione; D006892:Hydroxydopamines / Q000378:metabolism* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D009474:Neurons / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism*; D012710:Serum Albumin, Bovine; D013438:Sulfhydryl Compounds
D006892:Hydroxydopamines; D011506:Proteins; D013438:Sulfhydryl Compounds; D012710:Serum Albumin, Bovine; D005978:Glutathione; D003545:Cysteine