The proposed mechanism of iodothyronine deiodinase inhibition by the thiourea‐derived drugs 6‐n‐propylthiouracil (PTU) and 6‐methylthiouracil is supported by experimental evidence. Model reactions with sterically or coordinatively stabilized organoselenyl iodides as enzyme‐mimetic substrates (E‐SeI; see scheme) support the proposal that PTU reacts not with the enzyme but with the enzyme–SeI intermediate containing a covalent Se−I bond, and suggest that the Se−I bond is kinetically activated by basic amino acid groups such as histidine.

No abstract

Keywords: Phosphane selenide dibromides / Heteronuclear NMR / Raman spectroscopy / X-ray structures / Bromine exchange / Ab initio calculations

Enzyme mimetic studies on the crucial intermediate (E-SeI) of the iodothyronine deiodinase cycle have been carried out by using an areneselenenyl iodide stabilized by intramolecular Se.N interactions. Treatment of this compound with aromatic thiols and thiobenzoxazole in the presence of NEt(3) affords areneselenenyl sulfides that are stable towards disproportionation reactions. The structures of three of the areneselenenyl sulfides were determined by X-ray crystallography. In one case, in the absence of NEt(3), a diselenide can be formed rather than the selenenyl sulfide. The areneselenenyl iodide also reacts with a related selenol to produce the corresponding diselenide, and this reaction is found to be much faster than that with thiols. The high reactivity of the selenenyl iodide with the selenol suggests that a reduced selenol group (R'-SeH) may react with the E-SeI intermediate to produce a diselenide (E-Se-Se-R') without any thiol cosubstrate. The intermediacy of selenenyl sulfides during the reduction of selenenyl iodide by thiols and its possible relevance to the iodothyronine deiodinase catalytic cycle is also described.

Dedicated to Professor Reinhard Schmutzler on the occasion of his 70th birthdayThe biological role of nitric oxide (NO) as a secondary messenger, for instance in the cardiovascular system, has been known for more than a decade. Nitrosation of the cysteine