Molecular Aspects of Methylcadmium Toxicity: Effects on the H ₂ O ₂ 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.