STUDIES OF POSITIVE IODINE COMPOUNDS AS MODELS OF THE THYROIDAL "ACTIVE IODINE": REACTION OF N-IODOSUCCINIMIDE AND OF N-IODOPHTALIMIDE WITH THIOCARBAMIDE GOITROGENS

Ludk Jirousek ¹ and Morris Soodak ¹

¹ Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts

N-iodoimides were studied as interesting new models of the thyroidal "active iodine." They have been shown to react with goitrogenic thiocarbamides to form thiocarbamide sulfenyl iodide derivatives as reaction intermediates. Nongoitrogenic carbamides and other chemical analogs were unreactive. The overall oxidation of thiocarbamides by N-iodoimides in dimethylsulfoxide takes place in two stages: an initial very fast reaction followed by a much slower process. Kinetic and stoichiometric data for the fast reaction show that aromatic thiocarbamides (thiouracils, thiobarbiturates, etc.) are oxidized within this stage to disulfides, whereas aliphatic ones (thiourea and substituted thioureas) are oxidized to unknown products, probably tetravalent and hexavalent sulfur derivatives. The sulfenyl iodide intermediates were formed with both types of thiocarbamides. Structural considerations indicate an influence of mesomerisms in the thiocarbamides on the overall reaction pathway, but both thiol and thion forms were reactive with the positive iodine. Some potent goitrogens, e.g., 1-methyl-2-mercaptoimidazole, were not significantly oxidized beyond the disulfide stage. Since the behavior of N-iodoimides imitates that of the thyroidal "active iodine" more closely than l₂ does, these studies provide new insight on the mechanism of goitrogenic action. It is thought that the trapping of positive iodine is more important than the possible subsequent redox reactions.