SOME METAL CHELATE COMPOUNDS OF ETHYLENEDIAMINETETRAACETIC ACID

The inorganic salts of antimony, arsenic and bismuth are toxic substances, but their hard dissociated organic derivatives are less toxic and are widely used in the- rapy. Organic chelating compounds such as ethylenediaminetetraacetic acid (I) are often used as agents for detoxification of heavy metals. It appears that complexes formed by therapeutic metals and ethylenediaminetetraacetic acid would be less toxic as well and might be useful therapeutically. Such compounds have been prepared in the present work. Attempts to react ethylenediaminetetraacetic acid or its mono, di or tetra-sodi- um salts with freshly precipitated antimonous oxide were not successful. The former also failed to react with potassium antimonyltartrate. Treatment of antimony trichloride on aqueous ethylenediaminetetraacetic acid, however, gave a complex, which could be recrystallized from water without hydrolysis, and which gave no precipitate with catechol or rhodizonic acid. This complex forming reaction is most favourable at a pH of about 2.5. Neutralization of the complex with various alkalis or amines afforded the corresponding potassium, sodium, lithium, ammonium, ethylenediammonium and diethylammonium salts, which are water-soluble. Neither antimony pentachloride nor arsenic trichloride gave the corresponding chelating compounds with ethylenediaminetetraacetic acid under similar conditions. A bismuth chelate was formed by interaction of bismuth basic carbonate and aqueous ethylenediaminetetraacetic acid at 80°. This sparingly soluble chelate gave water-soluble salts on treatment with sodium hydroxide or ammonia. In order to study its structure, a pseudo-ephedrine salt, m. p. 270-271° (decomp.), (α)_D¹⁰=-1.28,° was prepared. Recrystallization of this salt, however, did not cause change in optical rotation. Structure II should give optical isomers. An alternative symme- trical structura was recently suggested by Japanese authors. It was shown in our previous work that stannous tin could yield potential therapeutic compounds. Attempts were therefore made to prepare a stannous chelate of ethylenediaminetetraacetic acid. Although treatment of the latter with stannous oxide did not afford a pure compound, its disodium salt and stannous chloride interacted smoothly in water and a chelate was formed. This new com- pound gave no precipitate on treatment with alkalis, oxalate or sodium thiosulphate, but it could reduce mercuric salts, and metallic tin was separated on treatment with zinc. A water-soluble diammonium salt was prepared. Oxidation of the stannous chelate of ethylenediaminetetraacetic acid by means of hydrogen peroxide afforded the corresponding stannic chelate. Since it could not be dehydrated under reduced pressure and its aqueous solution was distinctly acidic, its structure was assumed as a tetradentate ligand (Ⅲ) rather than a hexadentate one (Ⅳ). It was recently shown by Indian authors that tervalent metals did not necessarily give hexadentate ligand chelates. The stannic chelate is less stable toward alkali than the stannous compound. Preliminary pharmacological tests revealed that the sodium salt of the antimony chelate was as active as tartar emetic against schistosomiasis japonica in white mice.