A Possible Mechanism for Thiourea-Based Toxicities:  Kinetics and Mechanism of Decomposition of Thiourea Dioxides in Alkaline Solutions

Abstract

The decomposition kinetics of a series of thiourea dioxides has been studied in alkaline media. In aerobic conditions the decomposition is characterized by an induction period, which is followed by the formation of dithionite, S 2 O 4 2-. The rates of consumption of the thiourea dioxide and the formation of dithionite follow zero-order kinetics. No dithionite is formed in anaerobic conditions, although the thiourea dioxides can still rapidly decompose in the absence of oxygen to give sulfite and a urea as the decomposition products. No dithionite is formed until all the dioxygen in solution has been consumed, and hence the induction time is determined by the initial oxygen concentration in solution. A comprehensive mechanism that can adequately explain the decomposition is proposed in which the initial step is the cleavage of the C-S bond to give a urea residue and the sulfoxylate ion, SO 2 2-. The sulfoxylate ion is next rapidly oxidized by oxygen to give the anion radical, SO 2 -, which is the precursor to the formation of dithionite via a rapid equilibrium. In aerobic environments the sufoxylate ion can produce the highly tissue-damaging series of reactive oxygen species superoxide, peroxide, and hydroxyl radical. These species could be responsible for the inherent toxicities associated with thioureas.

Oxidation of a Dimethylthiourea Metabolite by Iodine and Acidified Iodate: N,N‘-Dimethylaminoiminomethanesulfinic Acid ()

“…Both the protonated and unprotonated forms of DMAIMSA can decompose to give a urea residue and a reactive radical sulfur leaving group. This decomposition was confirmed in an earlier study from our laboratory (30,31).…”

Mechanism Involving Hydrogen Sulfite Ions, Chlorite Ions, and Hypochlorous Acid as Key Intermediates of the Autocatalytic Chlorine Dioxide–Thiourea Dioxide Reaction

“…To pave the way towards detailed mechanistic insights into the chlorite-TU reaction, knowledge of the kinetics and mechanism of the title reaction is eagerly anticipated. Owing to the formation of SO 2 H -/SO 2 2-ions from the rapid decomposition of TDO in alkaline solutions, [5,6] TDO has been extensively applied in chemistry and chemical technology as a special and effective reducing agent, [7][8][9][10] especially for the potential chemical reduction of graphene oxide in recent years. [11,12] Its reducing ability increases with aging in alkaline solution.…”

A new procedure for the spectrophotometric determination of nitrogen(II) oxide in solutions

“…Previously, it was demonstrated in [9,10] that the decomposition of alkaline solutions of thiourea dioxide saturated with air is accompanied by the formation of dithionite preceded by the induction period. Under anaerobic conditions and in acidic or neutral solutions, dithionite is not formed irrespective of the presence of oxygen.…”