Investigating the Chemistry of Selenium and Sulfur Species: Potential Roles in Biology

Selenium and sulfur are both of the chalcogen family and can be found in a number of mammalian proteins and enzymes. Both display similar biologic utility, often serving as nucleophiles (selenol (RSeH) and thiol (RSH)) and redox regulators. However, selenium is commonly considered to have ‘enhanced’ reactivity over thiols, making selenols both more potent nucleophiles and reductants than analogous thiols. This characteristic may make selenols preferential targets (over thiols) in some biological systems and/or signaling pathways. To gain more insight into this notion, comparison studies for the trapping of nitroxyl (HNO), a potential therapeutic for the treatment of heart failure, were performed for selenols and analogous thiols. The smallest of all thiol species is hydrogen sulfide (H2S), which has recently received much attention for its potential role as a small biological signaling molecule. Though the observed therapeutic functions of H2S are remarkable, the mechanisms of action for H2S are yet undefined. In biological systems, H2S can react with disulfides (RSSR), forming an equilibrated system with the corresponding hydropersulfide (RSSH) and thiol (RSH), making it difficult to distinguish the actions of one from the others. Interestingly, hydropersulfides (along with polysulfudes (RSSnSR) and hydropolysulfides (RSSnSH) have also been identified in a number of mammalian cells. This raises the question of whether H2S is actually responsible for the observed effects upon its administration or whether other polysulfur species are the actual effector molecules. For this reason, the chemistry of individual thiol, hydropersulfide and polysulfide/hydropolysulfide species were investigated and their reactivity compared