posted on 2024-03-13, 20:05authored byMeng-Han Tsai, Ying-Ting Lin
Previously, it was believed that methylation was the
body’s
primary method to detoxify inorganic arsenic. However, recent research
has shown that the metabolized intermediate known as MMAIII is more toxic than arsenite and arsenate, contradicting a previous
understanding. Another important question arises: is arsenical toxicity
truly caused by arsenic binding to proteins through arsenic thiol
adhesion? Based on the toxicity order of the experiment, with MMAIII being the most toxic, followed by arsenite, arsenate, DMAV, and MMAV, density functional theory (DFT) calculations
can provide a straightforward assessment of this issue. Our practice
captures all the transition states associated with a specific imaginary-frequency
vibration mode, including proton transfer and simultaneous departure
of leaving group. We have obtained the energy barriers for five arsenicals
reacting with thiol, alcohol, and amine separately. In addition to
energetic favorability, the following are the energy barriers for
arsenic’s reaction with thiol ranked from low to high: MMAIII (25.4 kcal/mol), arsenite (27.7 kcal/mol), arsenate (32.8
kcal/mol), DMAV (36.2 kcal/mol), and MMAV (38.3
kcal/mol). Results show that the toxicity of arsenicals is mainly
caused by their reaction with thiol rather than with alcohol or amine,
as supported by the trend of decreasing toxicity and increasing energy
barriers. Thus, this DFT calculation may confirm the paradigm that
arsenic–thiol adhesion is the primary cause of arsenic toxicity
in the body.