Modeling of the Passive Permeation of Mercury and Methylmercury Complexes Through a Bacterial Cytoplasmic Membrane

Cellular uptake and export are important steps in the biotransformation of mercury (Hg) by microorganisms. However, the mechanisms of transport across biological membranes remain unclear. Membrane-bound transporters are known to be relevant, but passive permeation may also be involved. Inorganic Hg^II and methylmercury ([CH₃Hg^II]⁺) are commonly complexed with thiolate ligands. Here, we have performed extensive molecular dynamics simulations of the passive permeation of Hg^II and [CH₃Hg^II]⁺ complexes with thiolate ligands through a model bacterial cytoplasmic membrane. We find that the differences in free energy between the individual complexes in bulk water and at their most favorable position within the membrane are ∼2 kcal mol^-1. We provide a detailed description of the molecular interactions that drive the membrane crossing process. Favorable interactions with carbonyl and tail groups of phospholipids stabilize Hg-containing solutes in the tail-head interface region of the membrane. The calculated permeability coefficients for the neutral compounds CH₃S-Hg^II-SCH₃ and CH₃Hg^II-SCH₃ are on the order of 10^-5 cm s^-1. We conclude that small, nonionized Hg-containing species can permeate readily through cytoplasmic membranes.