Noncatalytic Reductive Deiodination of Thyroid Hormones. Electrochemistry and Quantum Chemical Calculations

Abstract

Noncatalytic processes may occur spontaneously leading often to undesired products. Electrochemical measurements provide data for thermodynamic calculations. Cyclic voltammetry of thyroxine (T4) and 3,3’,5‐triiodothyronine (T3) in N,N‐dimethylformamide (DMF) and alkaline aqueous solutions of pH 10–14 on glassy carbon electrodes yielded the values of redox potentials for the reduction leading to deiodination of those thyroid hormones under noncatalytic conditions. The first step of T4 deiodination occurs in DMF at −1.93 V vs. Fc+/Fc and for T3 at −1.95 V, which was confirmed by quantum‐chemical calculations at DFT and DLPNO‐CCSD(T) levels. In alkaline aqueous solutions, owing to poor solubility of these compounds, it was possible to determine only approximate values equal to −1.6 to −1.7 V vs. Ag/AgCl for the first step of deiodination. The reduction potentials do not depend on pH under these conditions. As shown by calculations, further steps exhibit very close reduction potentials. The radicals formed as products of concerted dissociative electron transfer to T4 and T3 are relatively kinetically stable which leads to side reactions initiated by radicals in uncatalyzed deiodination processes.