Original Article:
Ligand-Substitution Reactions of the Tellurium Compound AS-101 in Physiological Aqueous and Alcoholic Solutions
Alon Silberman, et al.
Inorg. Chem. 2016, 55(21), 10847–10850.
10.1021/acs.inorgchem.6b02138
The tellurium compound AS101 (trichloro(dioxoethylene-O,O′) tellurate) is a potent immunomodulator with multiple protective therapeutic applications. Studies have shown that most of the biological activity of AS-101 is attributed to the key TeIV atom and its specific chemical interaction with cysteine thiol residues. The chemical mechanism by which AS-101 displaces its ligand with its target cysteine has never been investigated before.
Therefore, in this study, the researchers initiated a series of experiments aimed at investigating the chemical behavior of AS-101 in relevant aqueous/alcoholic biological solutions. The results showed that under the aqueous conditions of administration, AS-101 immediately undergoes a ligand substitution reaction with water to produce a stable hydrolyzed oxide anion product, which was identified as TeOCl3- for the first time. Furthermore, for the structure of AS-101 in propylene glycol (PG), after exposure to water, AS-101 still exists in its hydrolyzed form TeOCl3-. From the perspective of future inorganic tellurium drug design, the tellurium oxide moiety should be considered and evaluated as a reactive group for cysteine thiol substitution.
Chemicals Related in the Paper:
