Molecular Aspects of Methylcadmium Toxicity: Effects on the H₂O₂ Reduction by Cysteine and Selenocysteine Disclosed In Silico

Cadmium (Cd), like the other group 12 elements (Zn and Hg), has a high affinity for sulfur (S) and selenium (Se), a property that strongly influences its adverse biological effects. Although the symptoms of Cd toxicity are diverse, a common denominator is found in oxidative stress, resulting in the disruption of redox balance in cells and the proliferation of reactive oxygen species (ROS) and harmful radicals. Methylcadmium (CH3Cd+) is a convenient model to study Cd pro-oxidant activity in silico. In this work, the effect of CH3Cd+ on the peroxy-reducing potential of cysteine (Cys) and selenocysteine (Sec) is investigated at the ZORA-BLYP-D3(BJ)/TZ2P level and compared to our current knowledge on the analogous molecular aspects of methylmercury’s toxicity (CH3Hg+). Molecular docking simulations indicate that CH3Cd+ binds favorably to the catalytic sites of the GPx1 and TrxR1 enzymes. The short distances between the metal and Sec suggest that a nucleophilic attack by Se to Cd leading to the inhibition of the enzyme is indeed possible. Methylcadmium pro-oxidant activity isif not equalonly slightly inferior to that of methylmercury.